Prevalencia y letalidad de enfermedades pulmonares intersticiales en la Región de Los Ríos, Chile / Prevalence and lethality of interstitial pulmonary diseases in the Region of Los Ríos, Chile

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a subtype of interstitial lung disease (ILD) that significantly affects people's quality of life, whose prevalence and mortality has increased. AIM: To determine the prevalence and lethality of ILD in the Los Ríos Region between the years 2018 and 2019. MATERIAL AND METHODS: Review of a database of all patients attended at an outpatient clinic of the regional hospital. Those patients with the diagnosis of ILD and seen between 2018 and 2019 were selected. Mortality and its causes were verified with death certificates. RESULTS: In the study period, 339 cases with ILD, aged 71 ± 10 years (64% women) were identified. The calculated ILD prevalence was 84 cases per 100,000 inhabitants, with a higher predominancy in Futrono and Paillaco communes. IPF and Connective Tissue Diseases were the predominant subtypes. Overall lethality was 18%, with more deaths among patients with IPF (n = 31). CONCLUSIONS: In the Los Ríos Region, ILDs have a relevant prevalence and lethality.

Correlaciones entre el test de velocidad en 4 metros y el test de caminata en 6 min en enfermos respiratorios crónicos / Correlations between the 4 meter speed test and the 6-minute walking test in chronic respiratory patients

Resumen La prueba de velocidad de marcha en 4 metros (T4M) es considerada sustituto de la caminata en 6 min (TC6M) en EPOC. Sin embargo, no ha sido bien investigada en otras enfermedades respiratorias. Durante un año estudiamos pacientes que concurrieron a nuestra Unidad para realizar el TC6M midiendo la velocidad alcanzada en 4 metros, 2 h previo a realizar el TC6M. De 162 pacientes 99 eran mujeres. La edad media fue de 65 años, peso de 73 kg, talla de 158 cm, IMC 29,4 kg/m2. 36% tenían fibrosis pulmonar idiopática, 17% EPOC, GOLD IV,11% EPOC, GOLD III, 12% apnea de sueño y 12% otras enfermedades. No hubo diferencia para los distintos diagnósticos en ambos tests. La distancia media en TC6Mfue 368,5 m la velocidad: 1,01 m/s en T4M.Hubo una correlación positiva significativa entre ambos test: alto rendimiento en T4M es equivalente a un alto rendimiento en el TC6M. Hubo correlación negativa con la edad y positiva con la estatura. Al año de seguimiento 16 pacientes habían fallecido, siendo estos los que habían obtenido los más bajos rendimientos en ambos tests (T4M: 0,69 m/s y 248,1 m en TC6M) La posibilidad de sobrevida cayó a 20% en aquellos individuos que alcanzaron una velocidad inferior a 0,69 m/s. Es posible sustituir el TC6M por el T4M en pacientes con diferentes patologías respiratoria, podemos predecir la muerte por cualquier causa si un sujeto camina a una velocidad ≤ 0,69 m/s, T4M es barato y fácil de realizar en atención primaria, sirviendo como evaluación de riesgo para referir a un centro más complejo.

4-Meter Gait Speed Test (4MGST) a frailty test, is considered a surrogate for the 6-Minute Walk Test (6MWT) in COPD. However, it has not been investigated in other respiratory conditions. Over a year, we studied patients attending our Unit for evaluation with 6MWT, measuring the speed they achieved walking 4 m, 2 h before performing 6MWT. 162 patients (99 women) were studied; series' mean values were: age 65 years-old; body weight, 73 kg; height, 158 cm and BMI, 29.4 kg/m2. 36% of them had idiopathic pulmonary fibrosis, 17% GOLD IV COPD, 11% GOLD III COPD, 12% pulmonary arterial hypertension, 12% obstructive apnea-hypopnea syndrome, and 12% other conditions. ANOVA showed no difference between diagnostic categories for both test. Average score in 6MWT was 368.5 m and 1.01 m/s in 4MGST. Pearson correlation coefficient revealed significant positive correlation between results of both tests: high score in 4MGST is equivalent to high score in 6MWT. There was negative correlation with age and positive correlation with height. At one year follow-up, 16 patients had died. They obtained significantly lower scores in both tests (4MGST: 0.69 m/s and 6MWT: 248.1 m) Survival chance fell to 20% for patients walking slower than 0.69 m/s. It is possible to replace TC6M with T4M in patients with different respiratory pathologies, we can predict death for any cause if a subject walked at ≤ speed at 0.69 m/s. T4M is cheap and easy to perform in primary care, serving as a risk assessment to refer to a more complex center.

Transplante pulmonar em pacientes com fibrose pulmonar familiar / Lung transplant in patients with familial pulmonary fibrosis

RESUMO Objetivo A fibrose pulmonar familiar (FPF) é definida como uma doença pulmonar intersticial idiopática que afeta dois ou mais membros da mesma família. Nesses pacientes, os resultados têm sido insatisfatórios, apresentando alto risco de morte e disfunção crônica do enxerto pulmonar (CLAD) após o transplante de pulmão. O objetivo do presente estudo foi comparar o resultado de curto e longo prazo do transplante de pulmão em pacientes com FPF e pacientes transplantados por outras doenças pulmonares intersticiais. Métodos Foram coletados retrospectivamente dados clínicos pré e pós-transplante de 83 pacientes com fibrose pulmonar submetidos a transplante de pulmão. Os pacientes foram divididos em aqueles com fibrose pulmonar familiar (n = 9, grupo FPF) e aqueles com fibrose pulmonar não familiar (n = 74, grupo controle). Resultados O grupo FPF foi composto de quatro mulheres e cinco homens, sendo 44,5% ex-fumantes. A maioria apresentou tomografia computadorizada e evidência patológica de pneumonia intersticial usual. Os pacientes com FPF tiveram níveis significativamente menores de hemoglobina e hematócrito. Não foram observadas outras diferenças nas características pré e pós-transplante em relação ao grupo controle. A evolução clínica pós-operatória foi semelhante nos dois grupos. Não foi constatada diferença significativa na sobrevida de um ano livre de CLAD e na sobrevida em geral. Conclusão A evolução pós-transplante de pacientes com FPF foi semelhante à dos pacientes com fibrose pulmonar não familiar, embora mais pacientes com FPF tivessem anemia pré-transplante. O resultado a curto e longo prazo foi comparável em ambos os grupos. O transplante de pulmão provou ser uma opção válida para pacientes com FPF, assim como para pacientes com outros tipos de fibrose pulmonar.

ABSTRACT Objective Familial pulmonary fibrosis (FPF) is defined as an idiopathic interstitial lung disease affecting two or more members of the same family; poor outcome with high risk of death and chronic lung allograft dysfunction (CLAD) after lung transplant has been reported in these patients. The present study aimed to compare the short- and long-term outcome of lung transplants in patients with FPF and patients transplanted because of other interstitial lung diseases. Method Clinical pre- and post-transplant data from 83 consecutive patients with pulmonary fibrosis who underwent lung transplant at our centre were collected retrospectively. Patients were divided into those with familial (n=9 FPF group) and those with non-familial pulmonary fibrosis (n=74 controls). Results The FPF group was composed of 4 females and 5 males; 44.5% were ex-smokers. The majority presented their CT scan and pathology evidence of usual interstitial pneumonia. Patients with FPF had significantly lower pre-transplant levels of haemoglobin and haematocrit. No other differences in pre- and post-transplant characteristics were observed concerning controls. The clinical post-operative course was similar in the two groups. No significant difference in one-year CLAD-free survival and overall survival was observed. Conclusion The post-transplant course of patients with FPF was similar to patients with non-familial pulmonary fibrosis, although more patients with FPF had pre-transplant anaemia. Short- and long-term outcome was comparable in both groups. Lung transplant proved to be a valid option for patients with FPF as it was for patients with other types of pulmonary fibrosis.

Padrões de tomografia computadorizada de alta resolução na doença pulmonar intersticial (DPI): prevalência e prognóstico / High resolution computed tomography patterns in interstitial lung disease (ILD): prevalence and prognosis

RESUMO Objetivo Correlacionar a prevalência e o prognóstico de cada padrão de TCAR de pneumonia intersticial usual (PIU) típica, provável e indeterminada com o diagnóstico clínico multidisciplinar de doença pulmonar intersticial (DPI). Métodos Incluímos todos os pacientes com diagnóstico multidisciplinar de DPI com padrão de TCAR de PIU típica, PIU provável ou indeterminada para PIU. Dados clínicos e histopatológicos, teste de função pulmonar e status de sobrevida foram obtidos retrospectivamente. O diagnóstico final foi validado por uma equipe multidisciplinar. Resultados Foram incluídos no estudo 244 pacientes, com média de idade de 68 ± 13 anos sendo 52,5% do sexo masculino. Em um total de 106 pacientes com padrão típico de PIU, 62% tiveram o diagnóstico multidisciplinar de FPI, 20% de pneumonia por hipersensibilidade crônica (PHC) e 10% de DPI relacionada à doença do tecido conjuntivo (DPI-DTC). Dos 114 casos com provável PIU, DPI-DTC correspondeu a 39%, FPI a 31%, pneumonia intersticial descamativa a 11%, doença pulmonar relacionada a medicamentos a 9% e PHC a 8%. Nos 24 pacientes com TC indeterminada para PIU, o DPI-DTC foi o diagnóstico final em 33%, seguido por pneumonia intersticial descamativa (21%) e FPI (13%). Pacientes com PIU típica apresentaram maior probabilidade de morrer ou realizar transplante de pulmão no seguimento (17,9% e 11,3%, respectivamente). Conclusões FPI, PHC e DPI-DTC foram os principais diagnósticos diferenciais em pacientes com padrão de TCAR de PIU típica, provável e indeterminada. Pacientes com padrão de PIU típico na TCAR tiveram maior probabilidade de morrer ou realizar transplante de pulmão no seguimento.

ABSTRACT Objective To correlate the prevalence and prognosis of each HRCT pattern of typical, probable, and indeterminate usual interstitial pneumonia (UIP) with the clinical multidisciplinary diagnosis of interstitial lung disease (ILD). Methods We included all patients with a multidisciplinary diagnosis of ILD with an HRCT pattern of typical UIP, probable UIP, or indeterminate for UIP. Clinical and histopathological data, pulmonary function tests, and survival status were retrospectively obtained. The final diagnosis was validated by a multidisciplinary team. Results A total of 244 patients were included in the study, with a mean age of 68 ±13 years and being 52.5% males. In a total of 106 patients with typical UIP pattern, 62% had the multidisciplinary diagnosis of IPF, 20% had chronic hypersensitivity pneumonitis (CHP), and 10% had connective tissue disease-related ILD (CTD-ILD). Out of the 114 cases with probable UIP, CTD-ILD corresponded to 39%, IPF to 31%, desquamative interstitial pneumonia to 11%, drug-related lung disease to 9%, and CHP to 8%. In the 24 patients with CT indeterminate for UIP, CTD-ILD was the final diagnosis in 33%, followed by desquamative interstitial pneumonia (21%), and IPF (13%). Patients with typical UIP were more likely to die or had lung transplantation in the follow-up (17.9% and 11.3%, respectively). Conclusion IPF, CHP, and CTD-ILD were the main differential diagnoses in patients with HRCT patterns of typical, probable and indeterminate UIP. Patients with HRCT typical UIP pattern were more likely to die or had lung transplantation in the follow-up.

Brazilian guidelines for the pharmacological treatment of idiopathic pulmonary fibrosis. Official document of the Brazilian Thoracic Association based on the GRADE methodology / Diretrizes brasileiras para o tratamento farmacológico da fibrose pulmonar idiopática. Documento oficial da Sociedade Brasileira de Pneumologia e Tisiologia baseado na metodologia GRADE

ABSTRACT 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.

RESUMO 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.

Cuidados bucais em paciente com fibrose pulmonar idiopática sob cuidados paliativos. Relato de caso / Oral care in idiopathic pulmonary fibrosis patient in palliative care. Case report

A Fibrose Pulmonar Idiopática (FPI) é uma doença crônica do interstício pulmonar que se manifesta por fibrose progressiva com alta prevalência de insuficiência respiratória. Como toda doença crônica e progressiva, a FPI necessita de acompanhamento por uma equipe multiprofissional de Cuidados Paliativos (CP) a fim de proporcionar um cuidado integral, considerando todas as queixas e necessidades do paciente. Em uma enfermaria de CP de um hospital terciário, um paciente do sexo masculino, 77 anos, foi admitido por FPI avançada para controle de sintomas e cuidados de fim de vida. Durante a oroscopia realizada pela equipe, recebeu diagnóstico de candidíase oral, onde foi solicitada avaliação do cirurgião-dentista. Na avaliação odontológica, queixou-se de língua ressecada e perda do paladar. Paciente acamado, dispneico em repouso, em uso contínuo de máscara de venturi e lábios ressecados, com presença de placas brancas ressecadas (resíduos alimentares) em palato duro e mole, mucosa jugal e gengival, língua ressecada com saburra e hipossalivação. Foi realizada a higiene oral, prescrição de substituto salivar e hidratante labial. O procedimento foi longo e intermitente devido à dificuldade do paciente de se manter sem o suporte de oxigênio. Após o procedimento, o paciente relatou melhora de 90% dos sintomas bucais. Conclusão: O caso apresentou as alterações bucais e os cuidados odontológicos em um paciente com FPI e também evidenciou a importância da avaliação especializada realizada pelo cirurgião-dentista inserido em uma equipe multiprofissional em CP, que, além do diagnóstico diferencial, proporcionou alívio dos sintomas bucais e conforto ao paciente em sua fase final de vida

Idiopathic Pulmonary Fibrosis (IPF) is a chronic interstitial lung disease manifested by progressive fibrosis with a high prevalence of respiratory failure. As all chronic and progressive diseases, IPF needs follow-up by a multidisciplinary Palliative Care (PC) team in order to provide comprehensive care considering all patient's complaints and needs. In a PC inpatient unit of a tertiary hospital, a 77-year-old male patient was admitted because of advanced IPF for symptom control and end-of-life care. During the oroscopy done by the team, he was diagnosed with oral candidiasis, where evaluation by the dentist was requested. In the dental evaluation, he complained of dry tongue and taste loss. Bedridden patient, dyspnea at rest, in continuous use of venturi mask and dry lips, dry white plaques (food residues) in hard and soft palate, jugal and gingival mucosa, dry tongue with oral coating and hyposalivation. Oral hygiene was performed, salivary substitute and lip moisturizer were prescribed. The procedure was long and intermittent due to the difficulty of the patient with staying without oxygen support. After the procedure, the patient reported 90% improvement in oral symptoms. Conclusion: The case showed the oral disorders and dental care in a patient with IPF and highlighted the importance of specialized evaluation performed by the dentist inserted in a multidisciplinary PC team which, besides the differential diagnosis, provided symptom relief of the mouth and comfort to the patient in his end of life

Trasplante pulmonar en pacientes con fibrosis pulmonar: experiencia del Instituto Nacional del Tórax / Lung transplantation in pulmonary fibrosis: an experience from National Institute of Thorax, Chile

Resumen La fibrosis pulmonar es una enfermedad progresiva y de mal pronóstico por lo que el trasplante pulmonar sigue siendo una opción para pacientes bien seleccionados. Objetivo: Evaluar resultados y sobrevida de pacientes con fibrosis pulmonar trasplantados a 8 años de inicio del programa de trasplante. Métodos: Estudio descriptivo de trasplantados de pulmón por fibrosis pulmonar desde agosto de 2010 a julio de 2018. Resultados: De un total de 76 trasplantes, un 68,4% han sido en pacientes con fibrosis pulmonar. La principal indicación fue fibrosis pulmonar idiopática (75%). El puntaje de priorización pulmonar (LAS) promedio fue de 53 y un 32% cumplía con criterios de urgencia. La edad promedio fue 55 años, y se usó técnica unipulmonar en un 98%. La principal complicación quirúrgica fue la estenosis bronquial (7,6%). De las complicaciones médicas precoces destacaron 26 episodios infecciosos y 6 rechazos celulares agudos. La principal complicación tardía fue la disfunción crónica de injerto. Los resultados funcionales promedio pre trasplante, a 1 y 3 años fueron: CVF de 49%, 71% y 70% del valor teórico. Un 40% ha fallecido en el período de seguimiento. La principal causa de mortalidad el primer año post trasplante fueron las infecciones. La sobrevida a 1, 3 y 5 años fue de 86,2%, 65,2% y 59,8% respectivamente. Conclusiones: En trasplante monopulmonar es una opción de tratamiento en estos pacientes, con una sobrevida de 59% a 5 años. Un tercio se trasplanta con criterios de urgencia, siendo las infecciones la principal complicación precoz y la disfunción crónica de injerto la complicación tardía más frecuente.

Pulmonary fibrosis is a progressive disease with a bad prognosis. This situation makes rise lung transplant as a therapeutic option among carefully selected patients. Objective: Evaluate the results and survival rates of patients with pulmonary fibrosis that were transplanted through an 8 years period of follow-up, from the beginning of our transplant program. Methods: Descriptive study of the transplanted patients diagnosed with pulmonary fibrosis from august 2010 to july 2018. Results: Out of 76 transplants, 68.4% were due to pulmonary fibrosis, among these, the main diagnosis was idiopathic pulmonary fibrosis (75%). The average lung allocation score (LAS) was 53 and 32% of them had urgency criteria. Patients ' age averaged 55 years-old and 98% of them underwent a single lung transplant. Early medical complications were seen in 26 patients with infectious episodes and 6 with acute rejection. The main late complication was chronic allograft dysfunction. The main surgical complication was bronchial stenosis (7.6%). In comparison to its base line reference values FVC means pre transplant and 1 and 3 years post-transplant were 49%, 70% and 71% respectively. A 40% of patients died during follow up period. Infections were the main cause of mortality during the first year. Survival rates at 1st 3rd and 5th year were 86,2%; 65.2% and 59.8% respectively. Conclusions: Single lung transplant is a therapeutic option for patients with interstitial lung disease with a 59% survival rate in 5 years, 1/3 fulfilled urgency criteria at the transplant time. The infections were the main early complication and chronic graft dysfunction was the main late complication.

Segurança e tolerabilidade de Nintedanibe em pacientes com fibrose pulmonar idiopática no Brasil / Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil

RESUMO Objetivo Ensaios clínicos mostraram que 150 mg de Nintedanibe duas vezes ao dia reduzem a progressão da doença em pacientes com Fibrose Pulmonar Idiopática (FPI), com um perfil de efeitos adversos que é controlável para a maioria dos pacientes. Antes da aprovação do Nintedanibe como tratamento para a FPI no Brasil, um Programa de Acesso Expandido (PEA) foi iniciado para fornecer acesso precoce ao tratamento e avaliar a segurança e a tolerância do Nintedanibe para este grupo de pacientes. Métodos Foram elegíveis para participar da PEA pacientes com diagnóstico de FPI nos últimos 5 anos, com capacidade vital forçada (CVF) ≥ 50% do previsto e capacidade de difusão dos pulmões para monóxido de carbono (DLco) 30%-79% do previsto. Os pacientes receberam Nintedanibe 150 mg, 2 vezes ao dia (bid). As avaliações de segurança incluíram eventos adversos que levaram à suspensão permanente do Nintedanibe e eventos adversos graves. Resultados O PEA envolveu 57 pacientes em 8 centros. A maioria dos pacientes era do sexo masculino (77,2%) e brancos (87,7%). No início do estudo, a média de idade foi de 70,7 (7,5) anos e a CVF foi de 70,7 (12,5%) do previsto. A média de exposição ao Nintedanibe foi de 14,4 (6,2) meses; a exposição máxima foi de 22,0 meses. Os eventos adversos frequentemente relatados pelo pesquisador como relacionados ao tratamento com Nintedanibe foram diarreia (45 pacientes, 78,9%) e náusea (25 pacientes, 43,9%). Os eventos adversos levaram à suspensão permanente do Nintedanibe em 16 pacientes (28,1%) que passaram por um evento adverso grave. Conclusões No PEA brasileiro, o Nintedanibe apresentou um perfil aceitável de segurança e tolerância em pacientes com FPI, condizendo com dados de ensaios clínicos.

ABSTRACT 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.

Mortality from idiopathic pulmonary fibrosis: a temporal trend analysis in Brazil, 1979-2014 / Mortalidade por fibrose pulmonar idiopática: análise temporal no Brasil, 1979-2014

ABSTRACT Objective: To analyze mortality from idiopathic pulmonary fibrosis (IPF) in Brazil over the period 1979-2014. Methods: Microdata were extracted from the Brazilian National Ministry of Health Mortality Database. Only deaths for which the underlying cause was coded as International Classification of Diseases version 9 (ICD-9) 515 or 516.3 (until 1995) or as ICD version 10 (ICD-10) J84.1 (from 1996 onward) were included in our analysis. Standardized mortality rates were calculated for the 2010 Brazilian population. The annual trend in mortality rates was analyzed by joinpoint regression. We calculated risk ratios (RRs) by age group, time period of death, and gender, using a person-years denominator. Results: A total of 32,092 deaths were recorded in the study period. Standardized mortality rates trended upward, rising from 0.24/100,000 population in 1979 to 1.10/100,000 population in 2014. The annual upward trend in mortality rates had two inflection points, in 1992 and 2008, separating three distinct time segments with an annual growth of 2.2%, 6.8%, and 2.4%, respectively. The comparison of RRs for the age groups, using the 50- to 54-year age group as a reference, and for the study period, using 1979-1984 as a reference, were 16.14 (14.44-16.36) and 6.71 (6.34-7.12), respectively. Men compared with women had higher standardized mortality rates (per 100,000 person-years) in all age groups. Conclusion: Brazilian IPF mortality rates are lower than those of other countries, suggesting underdiagnosis or underreporting. The temporal trend is similar to those reported in the literature and is not explained solely by population aging.

RESUMO Objetivo: Analisar a mortalidade por fibrose pulmonar idiopática (FPI) no Brasil no período de 1979-2014. Métodos: Foram extraídos microdados do Sistema de Informações de Mortalidade do Ministério da Saúde cuja causa básica de óbito tenha sido codificada conforme a Classificação Internacional das Doenças, 9ª edição, códigos 515 ou 516.3 (até 1995), e 10ª versão, código J84.1 (a partir de 1996). Os coeficientes de mortalidade padronizados foram calculados para a população brasileira de 2010. A tendência anual da mortalidade foi analisada pelo método de regressão por pontos de inflexão. Foram calculadas as razões de risco (RR) por faixa etária, período analisado e gênero, utilizando-se como denominador pessoas-ano. Resultados: Foram registrados 32.092 óbitos no período estudado. O coeficiente de mortalidade padronizado mostrou-se ascendente, passando de 0,24/100.000 habitantes em 1979 para 1,10/100.000 em 2014. A tendência anual de crescimento identificou dois pontos de inflexão, em 1992 e 2008, gerando três retas com crescimento anual percentual de 2,2%, 6,8% e 2,4%, respectivamente. As RR (IC95%) por faixa etária, elegendo a faixa de 50-54 anos como referência, e por período estudado, elegendo o período de 1979-1984 como referência, foram de 16,14 (14,44-16,36) e de 6,71 (6,34-7,12), respectivamente. Homens, comparados a mulheres, apresentaram taxas de mortalidade padronizadas (por 100.000 pessoas-ano) superiores em todas as faixas etárias. Conclusões: Os coeficientes de mortalidade brasileiros por FPI são inferiores aos de outros países, podendo indicar subdiagnóstico ou subnotificação. A tendência temporal é semelhante à descrita na literatura e não é justificada apenas pelo envelhecimento populacional.

Fibrosis pulmonar idiopática, tratamiento con pirfenidona / Idiopathic pulmonary fibrosis, treatment with pirfenidone

La fibrosis pulmonar idiopática es el tipo más frecuente de neumonía intersticial se caracteriza por un proceso de cicatrización anormal, con exceso de tejido fibroso. Es una patología crónica, progresiva, limitada a los pulmones de etiología desconocida que afecta a adultos mayores de 50 años con un deterioro progresivo de la función pulmonar y del intercambio gaseoso con un pronóstico fatal en un periodo relativamente corto. Se ha publicado un nuevo documento de consenso de la ATS/ERS/JRS/ALAT, sobre el diagnóstico y tratamiento de esta patología y se ha recomendado como tratamiento un fármaco nuevo que ha generado grandes expectativas, la pirfenidona, el cual posee propiedades antiinflamatorias y antifibróticas con resultados prometedores. Presentamos el caso clínico, de una paciente de 60 años de edad que ingresa al Hospital Seguro Social Universitario con un cuadro respiratorio insidioso; durante su internación fue diagnosticada de fibrosis pulmonar idiopática con criterios clínicos, imagenológicos e histológico. Se inició tratamiento con Pirfenidona según la recomendación del consenso; la evolución y seguimiento al quinto mes de tratamiento fue favorable.

Idiopathic pulmonary fibrosis is the most frequent type of interstitial pneumonia. It is characterized by an abnormal healing process, with excess fibrous tissue. It is a chronic, progressive illness, limited to the lungs with unknown etiology; it affects adults over 50 years old, with a progressive deterioration of lung function and gas exchange and a fatal outcome in a relatively short period. It has been published a new consensus document of the ATS/ERS/JRS/ALAT, about the diagnostic and treatment of these disease, and it is been suggested as a treatment a new drug that has generated great expectations, pirfenidone. It has anti-inflammatory and anti-fibrotic properties with promising results. we report the case of a patient of 60 years of age admitted to university hospital social security with an insidious respiratory symptoms, during her hospitalization she was diagnosed with idiopathic pulmonary fibrosis with clinical imaging and histopathological criteria. Treatment with Pirfenidone was initiated as recommended by consensus; monitoring the evolution and the fifth month of treatment was favorable.

Update on diagnosis and treatment of idiopathic pulmonary fibrosis / Atualização no diagnóstico e tratamento da fibrose pulmonar idiopática

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.

Functional improvement in patients with idiopathic pulmonary fibrosis undergoing single lung transplantation / Melhora funcional em portadores de fibrose pulmonar idiopática submetidos a transplante pulmonar unilateral

AbstractObjective: To evaluate the changes in lung function in the first year after single lung transplantation in patients with idiopathic pulmonary fibrosis (IPF).Methods: We retrospectively evaluated patients with IPF who underwent single lung transplantation between January of 2006 and December of 2012, reviewing the changes in the lung function occurring during the first year after the procedure.Results: Of the 218 patients undergoing lung transplantation during the study period, 79 (36.2%) had IPF. Of those 79 patients, 24 (30%) died, and 11 (14%) did not undergo spirometry at the end of the first year. Of the 44 patients included in the study, 29 (66%) were men. The mean age of the patients was 57 years. Before transplantation, mean FVC, FEV1, and FEV1/FVC ratio were 1.78 L (50% of predicted), 1.48 L (52% of predicted), and 83%, respectively. In the first month after transplantation, there was a mean increase of 12% in FVC (400 mL) and FEV1 (350 mL). In the third month after transplantation, there were additional increases, of 5% (170 mL) in FVC and 1% (50 mL) in FEV1. At the end of the first year, the functional improvement persisted, with a mean gain of 19% (620 mL) in FVC and 16% (430 mL) in FEV1.Conclusions: Single lung transplantation in IPF patients who survive for at least one year provides significant and progressive benefits in lung function during the first year. This procedure is an important therapeutic alternative in the management of IPF.

ResumoObjetivo: Avaliar as alterações de função pulmonar no primeiro ano após transplante de pulmão unilateral em pacientes portadores de fibrose pulmonar idiopática (FPI).Métodos: Foi avaliada retrospectivamente a variação da função pulmonar de portadores de FPI submetidos a transplante pulmonar unilateral entre janeiro de 2006 e dezembro de 2012 no decorrer do primeiro ano após o procedimento.Resultados: Dos 218 pacientes submetidos a transplante pulmonar durante o período do estudo, 79 (36,2%) eram portadores de FPI. Desses 79 pacientes, 24 (30%) foram a óbito e 11 (14%) não realizaram espirometria ao final do primeiro ano. Dos 44 pacientes incluídos no estudo, 29 (66%) eram homens. A média de idade dos pacientes foi de 57 anos.Antes do transplante, as médias de CVF, VEF1 e relação VEF1/CVF foram de 1,78 l (50% do previsto), 1,48 l (52% do previsto) e 83%, respectivamente. No primeiro mês após o transplante, houve um aumento médio de 12% tanto na CVF (400 ml) como no VEF1 (350 ml). No terceiro mês após o transplante, houve um aumento adicional médio de 5% (170 ml) na CVF e de 1% (50 ml) no VEF1. Ao final do primeiro ano, a melhora funcional foi persistente, com um ganho médio de 19% (620 ml) na CVF e de 16% (430 ml) no VEF1.Conclusões: O transplante pulmonar unilateral em portadores de FPI que sobrevivam por pelo menos um ano proporciona importante e progressivo benefício na sua função pulmonar no decorrer do primeiro ano. Este procedimento é uma importante alternativa terapêutica no manejo da FPI.

Lung transplantation / Transplante pulmonar

ABSTRACT Lung transplantation is a globally accepted treatment for some advanced lung diseases, giving the recipients longer survival and better quality of life. Since the first transplant successfully performed in 1983, more than 40 thousand transplants have been performed worldwide. Of these, about seven hundred were in Brazil. However, survival of the transplant is less than desired, with a high mortality rate related to primary graft dysfunction, infection, and chronic graft dysfunction, particularly in the form of bronchiolitis obliterans syndrome. New technologies have been developed to improve the various stages of lung transplant. To increase the supply of lungs, ex vivo lung reconditioning has been used in some countries, including Brazil. For advanced life support in the perioperative period, extracorporeal membrane oxygenation and hemodynamic support equipment have been used as a bridge to transplant in critically ill patients on the waiting list, and to keep patients alive until resolution of the primary dysfunction after graft transplant. There are patients requiring lung transplant in Brazil who do not even come to the point of being referred to a transplant center because there are only seven such centers active in the country. It is urgent to create new centers capable of performing lung transplantation to provide patients with some advanced forms of lung disease a chance to live longer and with better quality of life.

RESUMO O transplante pulmonar é um tratamento mundialmente aceito para alguma pneumopatias avançadas, conferindo aos receptores maior sobrevida e melhor qualidade de vida. Desde o primeiro transplante realizado com sucesso em 1983, mais de 40 mil transplantes foram feitos em todo mundo. Destes, cerca de 700 foram no Brasil. No entanto, a sobrevida do transplante é menor do que a desejada, com altos índices de mortalidade relacionados à disfunção primária do enxerto, infecções e disfunção crônica do enxerto, principalmente sob a forma da síndrome da bronquiolite obliterante. Novas tecnologias têm sido desenvolvidas para aprimoramento das diversas etapas do transplante pulmonar. Para aumentar a oferta de pulmões, o recondicionamento pulmonar ex vivo vem sendo utilizado em alguns países, inclusive no Brasil. Para suporte avançado de vida no período perioperatório, equipamentos de oxigenação extracorpórea e de suporte hemodinâmico vêm sendo utilizado como ponte para o transplante em pacientes gravemente doentes em lista de espera e para manter pacientes vivos até a resolução da disfunção primária do enxerto pós-transplante. Existe uma demanda reprimida de pacientes que necessitam de transplante pulmonar no Brasil e que nem sequer chegam a ser encaminhados a um centro transplantador, pois só existem sete deles ativos no país. É urgente a criação de novos centros capazes de realizar transplante pulmonar para oferecer a pacientes com algumas pneumopatias avançadas uma chance de viver mais e com melhor qualidade de vida.

Angiotensin II type 1 and 2 receptors and lymphatic vessels modulate lung remodeling and fibrosis in systemic sclerosis and idiopathic pulmonary fibrosis

OBJECTIVE: To validate the importance of the angiotensin II receptor isotypes and the lymphatic vessels in systemic sclerosis and idiopathic pulmonary fibrosis. METHODS: We examined angiotensin II type 1 and 2 receptors and lymphatic vessels in the pulmonary tissues obtained from open lung biopsies of 30 patients with systemic sclerosis and 28 patients with idiopathic pulmonary fibrosis. Their histologic patterns included cellular and fibrotic non-specific interstitial pneumonia for systemic sclerosis and usual interstitial pneumonia for idiopathic pulmonary fibrosis. We used immunohistochemistry and histomorphometry to evaluate the number of cells in the alveolar septae and the vessels stained by these markers. Survival curves were also used. RESULTS: We found a significantly increased percentage of septal and vessel cells immunostained for the angiotensin type 1 and 2 receptors in the systemic sclerosis and idiopathic pulmonary fibrosis patients compared with the controls. A similar percentage of angiotensin 2 receptor positive vessel cells was observed in fibrotic non-specific interstitial pneumonia and usual interstitial pneumonia. A significantly increased percentage of lymphatic vessels was present in the usual interstitial pneumonia group compared with the non-specific interstitial pneumonia and control groups. A Cox regression analysis showed a high risk of death for the patients with usual interstitial pneumonia and a high percentage of vessel cells immunostained for the angiotensin 2 receptor in the lymphatic vessels. CONCLUSION: We concluded that angiotensin II receptor expression in the lung parenchyma can potentially control organ remodeling and fibrosis, which suggests that strategies aimed at preventing high angiotensin 2 receptor expression may be used as potential therapeutic target in patients with pulmonary systemic sclerosis and idiopathic pulmonary fibrosis. .

Calidad de vida en pacientes con fibrosis pulmonar idiopática / Quality of life in patients with idiopathic pulmonary fibrosis

La fibrosis pulmonar idiopática (FPI) es una enfermedad crónica que afecta principalmente a adultos a partir de la quinta década de la vida. Se caracteriza por la presencia de disnea progresiva, declinación funcional sostenida y una supervivencia media al diagnóstico menor de tres años. Hasta ahora, el foco del tratamiento ha sido la mejoría de la supervivencia, pero para muchos pacientes, una mejoría en la calidad de vida (QoL) es un objetivo más realista. A pesar del importante impacto que la enfermedad tiene sobre los aspectos físicos, emocionales y sociales, la investigación enfocada en la QoL es muy limitada. Actualmente, no existe ningún instrumento que esté totalmentevalidado como apropiado en la evaluación de la QoL específicamente en pacientes con FPI. Los instrumentos de medición genéricos que se han utilizado en los pacientes con FPI incluyen el instrumento de 100 ítems de la OMS (WHOQoL-100), la escala de calidad debienestar (QWB) y el instrumento de 36 ítems (SF-36), ninguno de los cuales fue diseñado específicamente para pacientes con FPI. En los estudios revisados, los pacientes con FPIpresentaron afectación de la HRQoL en casi todos los dominios de la vida, pero los más afectados fueron los relacionados con el funcionamiento físico, los síntomas y niveles de independencia. Se requiere de más investigaciones para aprender sobre cómo esta enfermedad afecta a nuestros pacientes, si se adaptan a su enfermedad a lo largo del tiempo y, si lo hacen, de qué manera. Además, se necesita demostrar si alguno de losinstrumentos de medición de QoL existentes es confiable y válido para evaluar la HRQoL a lo largo del tiempo en la población de pacientes con FPI.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease that primarily affects adults from the fifth decade of life. It is characterized by progressive dyspnea, sustained functional decline and survival of less than three years after diagnosis. So far, the treatment has focused on improving survival, but for many patients, an improvement in quality of life (QoL) is a more realistic goal. Despite the significant impact the disease has on physical, emotional and social features of the patient's life, research focused on QoL is very limited.Currently, there are no fully validated instruments appropriate for the specific evaluation of QoL in patients with IPF. Generic measurement tools used in patients with IPF include the WHO 100 items instrument (WHOQOL-100), the quality scale of well-being (QWB)and the 36 items instrument (SF-36), but none of them was designed specifically for patients with IPF. In the reviewed studies, patients with IPF showed impairment of the health related QoL in almost all aspects of life, but those related to physical functioning,symptoms and levels of independence were the most affected ones. More research is needed to learn about how this disease affects IPF patients, whether they adapt themselves to their disease over time, and if so, how. Furthermore, research needs to showwhether the QoL measurement tools available are reliable and valid measures for health related QoL over time among patients with IPF.

O uso de testes do degrau para a avaliação da capacidade de exercício em pacientes com doenças pulmonares crônicas / The use of step tests for the assessment of exercise capacity in healthy subjects and in patients with chronic lung disease

Os testes do degrau são utilizados para avaliar a capacidade física. Devido à diversidade desses testes, o objetivo desta revisão foi descrever os protocolos utilizados em indivíduos saudáveis e naqueles com doença pulmonar crônica. Os testes do degrau utilizados em indivíduos saudáveis tiveram várias modificações ao longo dos anos. Na maioria dos testes, a duração é variável (90 s-10 min), mas a altura do degrau (23,0-50,8 cm) e o ritmo (22,5-35,0 degraus/min) permanecem constantes durante todo o teste. Entretanto, a utilização de uma altura fixa e de ritmo constante pode deixar de promover uma intensidade de trabalho adequada para indivíduos com diferentes níveis de aptidão física, e, portanto, a carga de trabalho pode estar acima ou abaixo da capacidade individual. Dessa forma, os protocolos foram modificados com a introdução de mudanças na altura do degrau e no ritmo durante o teste. Desde o final dos anos 70, os testes do degrau têm sido utilizados em pacientes com doenças pulmonares crônicas. Os protocolos são diversificados, com ajustes na altura do degrau (15-30 cm), ritmo (autocadenciado ou externamente cadenciado) e duração (90 s-10 min). Entretanto, a diversidade desses protocolos e a variedade de desfechos estudados impedem a determinação do melhor protocolo a ser utilizado em indivíduos com doenças pulmonares crônicas. Parece que os protocolos mais curtos com elevado ritmo seriam mais adequados para avaliar a dessaturação de oxigênio relacionada ao exercício na doença pulmonar crônica. Testes limitados por sintomas seriam mais apropriados para avaliar a tolerância ao exercício. São necessários estudos comparando diferentes protocolos de teste do degrau em relação a sua reprodutibilidade, validade e habilidade de quantificar respostas a intervenções, especialmente em indivíduos com doença pulmonar.

Step tests are typically used to assess exercise capacity. Given the diversity of step tests, the aim of this review was to describe the protocols that have been used in healthy subjects and in patients with chronic lung disease. Step tests for use in healthy subjects have undergone a number of modifications over the years. In most step tests, the duration is variable (90 s-10 min), but the step height (23.0-50.8 cm) and stepping rate (22.5-35.0 steps/min) remain constant throughout the test. However, the use of a fixed step height and constant stepping rate might not provide adequate work intensity for subjects with different levels of fitness, the workload therefore being above or below individual capacity. Consequently, step test protocols have been modified by introducing changes in step heights and stepping rates during the test. Step tests have been used in patients with chronic lung diseases since the late 1970s. The protocols are quite varied, with adjustments in step height (15-30 cm), pacing (self-paced or externally paced), and test duration (90 s-10 min). However, the diversity of step test protocols and the variety of outcomes studied preclude the determination of the best protocol for use in individuals with chronic lung disease. Shorter protocols with a high stepping rate would seem to be more appropriate for assessing exercise-related oxygen desaturation in chronic lung disease. Symptom-limited testing would be more appropriate for evaluating exercise tolerance. There is a need for studies comparing different step test protocols, in terms of their reliability, validity, and ability to quantify responses to interventions, especially in individuals with lung disease.

Utilização de células-tronco derivadas da medula óssea: terapia viável para doenças pulmonares obstrutivas crônicas? / Use of bone marrow stem cells: feasible therapy for chronic obstructive pulmonary disease?

Doenças pulmonares obstrutivas crônicas acarretam em redução na qualidade de vida dos portadores e altos gastos ao sistema público de saúde. Na maioria dos casos, o tratamento destas enfermidades envolve apenas medidas paliativas, o que as tornam grandes alvos de pesquisa com terapia celular. As células-tronco têm capacidade de se diferenciar em todos os tecidos que compõem o organismo devido à plasticidade, e sua ação na regeneração tecidual é comprovada apesar do mecanismo não estar totalmente elucidado. Células-tronco foram, em princípio, pesquisadas como panacéias para doenças neurológicas, cardiovasculares e diabetes. Os resultados favoráveis à utilização dessa terapia nestes sistemas impulsionaram pesquisas em doenças pulmonares obstrutivas crônicas, como enfisema, fibrose cística e fibrose pulmonar idiopática.

Chronic obstructive pulmonary disease have been targets of cell therapy research, because they decrease life quality, cost a lot to the public health system and can only be treated with palliative protocols. The stem cells are capable of differentiating into all body tissues, according to their plasticity, and its action in tissue regeneration is established, although the mechanism is not fully elucidated. Stem cells were initially investigated as panaceas for diabetes as well as for neurological and cardiovascular diseases. The positive results obtained with stem cell therapy in these systems stimulated research about its use for treatment of chronic obstructive pulmonary diseases, such as emphysema, cystic fibrosis and idiopathic pulmonary fibrosis.