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A fibrose pulmonar idiopática (FPI) é uma forma de pneumopatia intersticial crônica fibrosante de causa desconhecida, que acomete preferencialmente homens idosos, com história atual ou pregressa de tabagismo. Mesmo sendo uma doença incomum, ela assume grande importância devido a sua gravidade e prognóstico reservado. Nas últimas décadas, diversas modalidades terapêuticas farmacológicas foram investigadas para o tratamento dessa doença, de tal modo que conceitos clássicos vêm sendo revisados. O objetivo destas diretrizes foi definir recomendações brasileiras baseadas em evidências em relação ao emprego de agentes farmacológicos no tratamento da FPI. Procurou-se fornecer orientações a questões de ordem prática, enfrentadas pelos clínicos no seu cotidiano. As perguntas PICO (acrônimo baseado em perguntas referentes aos Pacientes de interesse, Intervenção a ser estudada, Comparação da intervenção e Outcome [desfecho] de interesse) abordaram aspectos relativos ao uso de corticosteroides, N-acetilcisteína, tratamento medicamentoso do refluxo gastroesofágico, inibidores dos receptores da endotelina, inibidores da fosfodiesterase-5, pirfenidona e nintedanibe. Para a formulação das perguntas PICO, um grupo de especialistas brasileiros atuantes na área foi reunido, sendo realizada uma extensa revisão bibliográfica sobre o tema. As revisões sistemáticas com meta-análises previamente publicadas foram analisadas quanto à força das evidências compiladas e, a partir daí, foram concebidas recomendações seguindo a metodologia Grading of Recommendations Assessment, Development and Evaluation. Os autores acreditam que o presente documento represente um importante avanço a ser incorporado na abordagem de pacientes com FPI, objetivando principalmente favorecer seu manejo, e pode se tornar uma ferramenta auxiliar na definição de políticas públicas relacionadas à FPI. Idiopathic pulmonary fibrosis (IPF) is a form of chronic interstitial lung disease of unknown cause, which predominantly affects elderly men who are current or former smokers. Even though it is an uncommon disease, it is of great importance because of its severity and poor prognosis. In recent decades, several pharmacological treatment modalities have been investigated for the treatment of this disease, and the classic concepts have therefore been revised. The purpose of these guidelines was to define evidence-based recommendations regarding the use of pharmacological agents in the treatment of IPF in Brazil. We sought to provide guidance on the practical issues faced by clinicians in their daily lives. Patients of interest, Intervention to be studied, Comparison of intervention and Outcome of interest (PICO)-style questions were formulated to address aspects related to the use of corticosteroids, N-acetylcysteine, gastroesophageal reflux medications, endothelin-receptor antagonists, phosphodiesterase-5 inhibitors, pirfenidone, and nintedanib. To formulate the PICO questions, a group of Brazilian specialists working in the area was assembled and an extensive review of the literature on the subject was carried out. Previously published systematic reviews with meta-analyses were analyzed for the strength of the compiled evidence, and, on that basis, recommendations were developed by employing the Grading of Recommendations Assessment, Development and Evaluation approach. The authors believe that the present document represents an important advance to be incorporated in the approach to patients with IPF, aiming mainly to improve its management, and can become an auxiliary tool for defining public policies related to IPF.

Objective Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. Methods Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. Results The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. Conclusion In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.

Objective: To describe the clinical, functional, and radiological features of index cases of familial pulmonary fibrosis (FPF) in Brazil. Methods: We evaluated 35 patients with FPF - of whom 18 (51.4%) were women - with a median age of 66.0 years (range, 35.5-89.3 years). All of the patients completed a standardized questionnaire, as well as undergoing pulmonary function tests and HRCT of the chest. In 6 cases, lung tissue samples were obtained: from surgical biopsies in 5 cases; and from an autopsy in 1 case. Results: A history of smoking and a history of exposure to birds or mold were reported in 45.7% and 80.0% of the cases, respectively. Cough and marked dyspnea were reported by 62.8% and 48.6% of the patients, respectively. Fine crackles were detected in 91.4% of the patients. In 4 patients, the findings were suspicious for telomere disease. The median FVC and DLCO, as percentages of the predicted values, were 64.9% (range, 48.8-105.7%) and 38.9% (range, 16.0-60.0%), respectively. Nine patients had reduced DLCO despite having normal spirometry results. Regarding HRCT, patterns typical of usual interstitial pneumonia were found in 6 patients (17.1%). In 25 cases (71.5%), the HRCT features were consistent with a diagnosis other than idiopathic pulmonary fibrosis. In 11 cases (31.4%), the radiological patterns were uncharacteristic of interstitial lung disease. Of the six lung tissue samples analyzed, four showed interstitial pneumonia with bronchiolocentric accentuation, and, on the basis of the clinical and radiological data, the corresponding patients were diagnosed with hypersensitivity pneumonitis. Conclusions: Patients with FPF can present with a wide variety of clinical features. Most HRCT scans of these patients exhibit patterns not typical of usual interstitial pneumonia. The family history of fibrotic lung diseases should be investigated in all patients under suspicion, regardless of their age. RESUMO Objetivo: Descrever as características clínicas, funcionais e radiológicas de um grupo de casos índice diagnosticados com fibrose pulmonar familiar (FPF) no Brasil. Métodos: Trinta e cinco pacientes com FPF (18 mulheres; 51,4%), com mediana de idade de 66,0 anos (variação: 35,5-89,3 anos), responderam a um questionário padronizado e foram submetidos a testes de função pulmonar e TCAR de tórax. Tecido pulmonar foi obtido para revisão em 6 casos: a partir de biópsias cirúrgicas em 5 e de autópsia em 1. Resultados: Antecedentes de tabagismo e de exposição a aves ou mofo foram referidos por 45,7% e 80,0% dos casos, respectivamente. Tosse e dispneia significante foram referidas por 62,8% e 48,6% dos pacientes, respectivamente. Estertores finos foram detectados em 91,4% dos indivíduos. Em 4 pacientes, os achados levantaram suspeitas de doença dos telômeros. As medianas da CVF e da DLCO foram, respectivamente, de 64,9% (variação: 48,8-105,7%) e 38,9% (variação: 16,0-60,0%) em porcentagem dos valores previstos. Apesar de espirometria normal, 9 pacientes exibiram DLCO reduzida. Em relação às TCAR, padrões típicos de pneumonia intersticial usual foram encontrados em 6 pacientes (17,1%). Em 25 casos (71,5%) os achados tomográficos foram mais consistentes com um diagnóstico de não relacionado a fibrose pulmonar idiopática. Em 11 pacientes (31,4%) o padrão radiológico foi incaracterístico para doença pulmonar intersticial. Das seis amostras de tecido pulmonar analisadas, quatro mostraram pneumonias intersticiais com acentuação bronquiolocêntrica e, em função de outros dados clínicos e radiológicos, pneumonite de hipersensibilidade foi diagnosticada. Conclusões: Pacientes com FPF podem apresentar características clínicas diversas. A maioria das TCAR desses pacientes exibe padrões não típicos de pneumonia intersticial usual. A pesquisa da história clínica de outros casos de pneumopatias fibrosantes na família deve ser feita em todos os pacientes em investigação, independentemente da idade.

Idiopathic pulmonary fibrosis is a type of chronic fibrosing interstitial pneumonia, of unknown etiology, which is associated with a progressive decrease in pulmonary function and with high mortality rates. Interest in and knowledge of this disorder have grown substantially in recent years. In this review article, we broadly discuss distinct aspects related to the diagnosis and treatment of idiopathic pulmonary fibrosis. We list the current diagnostic criteria and describe the therapeutic approaches currently available, symptomatic treatments, the action of new drugs that are effective in slowing the decline in pulmonary function, and indications for lung transplantation. A fibrose pulmonar idiopática é um tipo de pneumonia intersticial crônica fibrosante, de causa desconhecida, associada à piora funcional respiratória progressiva e taxas elevadas de mortalidade. Em anos recentes, o interesse e os conhecimentos sobre essa moléstia têm aumentado substancialmente. O presente artigo de revisão aborda de maneira ampla aspectos relacionados ao diagnóstico e tratamento da doença. Nele são listados os critérios atuais para o diagnóstico e são discutidos as diferentes abordagens terapêuticas agora disponíveis, o tratamento sintomático, a ação de novas drogas eficazes em reduzir o ritmo de deterioração funcional pulmonar e as indicações para transplante pulmonar.