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.

Rendimiento diagnóstico y morbimortalidad de las biopsias pulmonares quirúrgicas en enfermedad pulmonar intersticial difusa

Introducción: Se denomina Enfermedad Pulmonar Intersticial Difusa (EPID) a un conjunto heterogéneo de patologías caracterizadas por inflamación y fibrosis pulmonar. El diagnóstico basado en patrones clínicos o radiológicos puede, ocasionalmente, ser insuficiente para iniciar un tratamiento. La biopsia pulmonar quirúrgica es una alternativa cuando se requiere aumentar la precisión diagnóstica luego de discusión multidisciplinaria. Objetivo: Describir el rendimiento diagnóstico, morbilidad y mortalidad de las biopsias quirúrgicas pulmonares en un hospital público chileno. Pacientes y Método: Cohorte retrospectiva de todos los pacientes a quienes se realizó biopsia quirúrgica por diagnóstico de EPID entre los años 2010 y 2020, indicada por un comité multidisciplinario. Se excluyen procedimientos similares o biopsias con diagnóstico de EPID como hallazgo incidental. Resultados: 38 pacientes intervenidos, mediana de edad de 63 años, 47% femenino. Solo 1 (2,6%) paciente operado de urgencia, y 34 (89,5%) por videotoracoscopía. 5 (13,1%) pacientes presentaron morbilidad, en 4 de ellos fuga aérea, ninguno requiriendo intervención adicional. No hubo rehospitalización, reoperación ni mortalidad a 90 días. En el 95% de los casos se alcanzó un diagnóstico preciso de la EPID tras discusión multidisciplinaria. Discusión: Se observa un alto rendimiento diagnóstico y una baja morbimortalidad en los pacientes estudiados. La baja frecuencia de procedimientos de urgencia y la adecuada indicación en comité multidisciplinario puede haber contribuido a la baja morbilidad. Conclusión: La biopsia pulmonar quirúrgica en un hospital general tiene un alto rendimiento diagnóstico cuando se discute en comité multidisciplinario para precisar el diagnostico en EPID, con una baja morbimortalidad si se seleccionan adecuadamente los pacientes.

Background: Interstitial Lung Disease (ILD) is a heterogeneous group of diseases characterized by inflammation and fibrosis of the lung. Diagnosis based exclusively on clinical or radiologic patterns may be inaccurate, and if a reliable diagnosis cannot be made, surgical lung biopsy can be strongly considered to increase the diagnostic yield after multidisciplinary committee. Objective: To review the diagnostic results, morbidity, and mortality of surgical biopsies in a chilean public health institution. Patients and Method: Retrospective cohort of patients operated for diagnostic purposes for ILD between 2010 - 2020. Surgical biopsies done for other diagnoses were excluded. Results: 38 patients were included, with a median age of 63 years, 47% were female. Only 1 patient (2.6%) underwent emergency surgery and 89.5% underwent minimally invasive surgery techniques. 5 patients had some morbidity (13.1%), 4 of them being air leak. All complications were successfully managed conservatively. We had no readmission, reoperations, or 90-day mortality in this cohort. In 95% of the cases an accurate diagnosis of ILD was reached after multidisciplinary discussion. Discussion: In our experience surgical lung biopsy has a high diagnostic yield and a low morbidity and mortality. A low number of emergency procedures and accurate surgical indication by an expert committee could explain the low morbidity. Conclusion: Surgical lung biopsy in a general hospital reach a high diagnostic performance when discussed in a multidisciplinary committee to specify the diagnosis in ILD, with low morbidity and mortality if patients are properly selected.

Risk factors of early death after lung transplantation in patients with idiopathic pulmonary fibrosis complicated with pulmonary arterial hypertension / 中华危重病急救医学

Objective:To investigate the risk factors of early death after lung transplantation in patients with idiopathic pulmonary fibrosis (IPF) complicated with pulmonary arterial hypertension (PAH).Methods:A retrospective cohort study was conducted. The clinical data of 134 patients with IPF and PAH who underwent lung transplantation at Wuxi People's Hospital Affiliated to Nanjing Medical University from January 2017 to December 2020 were collected. The donor's gender, age, duration of mechanical ventilation, and cold ischemia time, the recipient's gender, age, body mass index (BMI), smoking, history of hypertension and diabetes, preoperative usage of hormones, mean pulmonary arterial pressure (mPAP), cardiac echocardiography and cardiac function, serum creatinine (SCr), N-terminal pro-brain natriuretic peptide (NT-proBNP) as well as surgical type, extracorporeal membrane oxygenation (ECMO) treatment, duration of operation, and plasma and red blood cell infusion ratio were collected. The cumulative survival rates of patients at 30, 60, and 180 days after lung transplantation were calculated by Kaplan-Meier method. The univariate and multivariate Cox proportional hazards regression models were used to analyze the effects of donor, recipient, and surgical factors on early survival in donors after lung transplantation.Results:The majority of donors were male (80.6%). There was 63.4% of the donors older than 35 years old, 80.6% of the donors had mechanical ventilation duration less than 10 days, and the median cold ischemia time was 465.00 (369.25, 556.25) minutes. The recipients were mainly males (83.6%). Most of the patients were younger than 65 years old (70.9%). Most of them had no hypertension (75.4%) or diabetes (67.9%). The median mPAP of recipients was 36 (30, 43) mmHg (1 mmHg≈0.133 kPa). There were 73 patients with single lung transplantation (54.5%), and 61 with double lung transplantation (45.5%). The survival rates of 134 IPF patients with PAH at 30, 60, 180 days after lung transplantation were 81.3%, 76.9%, and 67.4%, respectively. Univariate Cox proportional risk regression analysis showed that recipient preoperative use of hormone [hazard ratio ( HR) = 2.079, 95% confidence interval (95% CI) was 1.048-4.128], mPAP ≥ 35 mmHg ( HR = 2.136, 95% CI was 1.129-4.044), NT-proBNP ≥ 300 ng/L ( HR = 2.411, 95% CI was 1.323-4.392), New York Heart Association (NYHA) cardiac function classification Ⅲ-Ⅳ ( HR = 3.021, 95% CI was 1.652-5.523) were the risk factors of early postoperative death in patients with IPF complicated with PAH (all P < 0.05). In the multivariable Cox proportional risk regression analysis, recipient preoperative hormone usage (model 1: HR = 2.072, 95% CI was 1.044-4.114, P = 0.037; model 2: HR = 2.098, 95% CI was 1.057-4.165, P = 0.034), NT-proBNP ≥ 300 ng/L ( HR = 2.246, 95% CI was 1.225-4.116, P = 0.009) and NYHA cardiac function classification Ⅲ-Ⅳ ( HR = 2.771, 95% CI was 1.495-5.134, P = 0.001) were independent risk factors of early postoperative death in patients with IPF. Conclusions:Preoperative hormone usage, NT-proBNP ≥ 300 ng/L, NYHA cardiac function classification Ⅲ-Ⅳ are independent risk factors for early death in patients with IPF and PAH after lung transplantation. For these patients, attention should be paid to optimize their functional status before operation. Preoperative reduction of receptor hormone usage and improvement of cardiac function can improve the early survival rate of such patients after lung transplantation.

Mechanism of Active Components of Chinese Medicine in Treatment of Idiopathic Pulmonary Fibrosis： A Review / 中国实验方剂学杂志

Idiopathic pulmonary fibrosis （IPF） is a progressive interstitial lung disease with unknown etiology and poor prognosis. At present， there are few antifibrotic drugs， which have limited efficacy and cause diverse side effects in the treatment of IPF， failing to meet the clinical needs. Therefore， it is urgent to develop more safe and effective drugs to treat IPF. Traditional Chinese medicine （TCM） has garnered increasing attention in recent years in the treatment of IPF due to its unique advantages. Increasing studies have shown that Chinese medicines have remarkable therapeutic effects on IPF and broad application prospects. However， the unclear material basis and mechanism in treating IPF hinders the modernization， internationalization， and clinical application of Chinese medicines. Therefore， it is essential to decipher the mechanism of the active components in Chinese medicines in treating IPF， which has gradually become a hot spot in the research on IPF. Increasing research results have demonstrated that anti-inflammation， anti-oxidation， inhibition of epithelial-mesenchymal transition are involved in the treatment of IPF with these active components， whereas the systematic research and summary remain to be carried out. By reviewing the articles about the treatment of IPF with the active components in Chinese medicines in recent years， this paper summarizes the mechanism and experimental studies and puts forward the existing problems in the research on the mechanism， aiming to provide references for the further basic research on IPF and the development of targerted drugs.

Effect of acute kidney injury on near-term prognosis of the recipients with idiopathic pulmonary fibrosis after lung transplantation / 中华器官移植杂志

Objective:To explore the effect of acute kidney injury(AKI)on near-term survival after lung transplantation(LT)in patients with idiopathic pulmonary fibrosis(IPF).Methods:Through consulting electronic medical records, anesthetic modes and Chinese Lung Transplant Registration System, clinical data are retrospectively reviewed for 275 IPF patients undergoing LT at Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2017 to April 2021.According to the diagnostic criteria of Kidney Disease: Improving Global Outcomes(KDIGO), they are divided into two groups of AKI(169 cases)and non-AKI(106 cases).Perioperative findings of two groups are recorded.Then univariate and multivariate Cox regression models are employed for determining whether or not inter-group differences existed in survival rates post-LT.Also AKI is staged according to the KDIGO.And the effect of stage 1/2/3 AKI on near-term postoperative prognosis is examined.Results:The differences are significantly different in recipient gender, creatinine, 6-minute walking test, forced vital capacity(FVC), lung allocation score, oxygenation index, N-terminal pro-brain natriuretic peptide(NT-Pro BNP), preoperative hormone use and volume of crystal infusion( P<0.05).After multivariate Cox regression correcting for covariates, no statistical significance exists in effect of AKI stage 1 on near-term postoperative survival rate( P<0.05).AKI stage 2/3 still has statistical significance in risk of mortality at Day 30/90/180/365 post-operation( P>0.05). Conclusions:As a common complication post-LT, AKI significantly affects near-term postoperative prognosis of transplant IPF patients.Stage 2/3 AKI impacts near-term postoperative survival while stage 1 AKI is not associated with higher mortality.

Effect of donor age on short-term survival of patients with idiopathic pulmonary fibrosis after lung transplantation / 器官移植

Objective To evaluate the effect of donor age on short-term survival of patients with idiopathic pulmonary fibrosis (IPF) after lung transplantation. Methods Clinical data of 235 IPF donors and recipients of lung transplantation were retrospectively analyzed. Univariate and multivariate Cox proportional hazard regression models were employed to analyze the correlation between donor age and short-term mortality rate of IPF patients after lung transplantation. Kaplan-Meier was used to draw the survival curve. Results Univariate Cox regression analysis showed that donor age was correlated with the 1-year fatality of IPF patients after lung transplantation. The 1-year fatality of recipients after lung transplantation was increased by 0.020 times if donor age was increased by 1 year (P=0.009). Oxygenation index of the donors, preoperative oxygenation index, preoperative lung allocation score, preoperative N-terminal pro brain natriuretic peptide, pattern of transplantation, pattern of intraoperative extracorporeal membrane oxygenation and intraoperative blood transfusion volume of the recipients were correlated with 1-year fatality after lung transplantation (all P < 0.1). Multivariate Cox regression analysis demonstrated that there was no correlation between donor age and 30-, 90-, 180-d and 1-year fatality of IPF patients after lung transplantation (all P > 0.05). Sensitivity analysis showed that there was no significant difference in 30-, 90-, 180-d and 1-year fatality after lung transplantation among donors aged < 18, 18-33, 34-49 and ≥50 years (all P > 0.05). Conclusions Donor age exerts no effect upon short-term survival of IPF patients after lung transplantation. Considering the mechanical ventilation time, oxygenation index, infection and other factors of donors, the age range of lung transplant donors may be expanded.

Medicated Serum of Bupleuri Radix Regulates HFL1 Apoptosis and Fibroblast-myofibroblast Transition via Smad3/Rheb Axis / 中国实验方剂学杂志

ObjectiveTransforming growth factor-β1 （TGF-β1） was used to stimulate human fetal lung fibroblast 1 （HFL1） for simulating the pathological process of idiopathic pulmonary fibrosis （IPF） and thereby the effects and mechanism of medicated serum of Bupleuri Radix against IPF were investigated. MethodTGF-β1 （10 μg·L-1） was employed to stimulate HFL1， and cells were treated with medicated serum of Bupleuri Radix （5%， 10%， 15%， 20%） for 24 h. Then cell proliferation rate was determined with cell counting kit-8 （CCK-8）. Subsequently， cells were classified into the control group （20% blank serum）， TGF-β1 group （20% blank serum and 10 μg·L-1 TGF-β1）， TGF-β1 + medicated serum of Bupleuri Radix group （5% blank serum， 15% medicated serum， and 10 μg·L-1 TGF-β1）， and TGF-β1 + SIS3 group （3 μmol·L-1 SIS3， 20% blank serum， 10 μg·L-1 TGF-β1）. Based on in situ end labeling （TUNEL） staining， the apoptosis rate was examined， and mRNA expression of apoptosis-related proteins B-cell lymphoma 2 （Bcl-2）， Bcl-2 associated X protein （Bax） and myofibroblast marker α-smooth muscle actin （α-SMA） was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression of α-SMA， Ras homolog enriched in brain （Rheb）， and phosphorylated （p）-Smad3 was determined by immunofluorescence. Expression of Rheb， p-Smad3， and Smad3 was examined by Western blot. ResultThe cell proliferation rate of TGF-β1 group increased compared with that of the control group （P<0.05）. The cell proliferation rate of TGF+15% medicated serum of Bupleuri Radix group and TGF+20% medicated serum of Bupleuri Radix group decreased compared with that of the TGF-β1 group （P<0.01）. Compared with the control group， TGF-β1 group showed decrease in apoptosis rate， increase in mRNA expression of Bcl-2 and α-SMA， reduction in Bax mRNA expression， and rise of α-SMA and Rheb protein expression and p-Smad3 level （P<0.05）. Compared with TGF-β1 group， TGF-β1 + medicated serum of Bupleuri Radix group and TGF-β1 + SIS3 group demonstrated high apoptosis rate， low Bcl-2 and α-SMA mRNA expression， high Bax mRNA expression， and low α-SMA and Rheb protein expression and p-Smad3 level （P<0.05）. ConclusionMedicated serum of Bupleuri Radix can inhibit TGF-β1-induced HFL1 proliferation and fibroblast-myofibroblast transition and promote fibroblast apoptosis by regulating the Smad3/Rheb axis.

S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

Biomechanical Characteristics of Idiopathic Pulmonary Fibrosis / 医用生物力学

Idiopathic pulmonary fibrosis (IPF) is a common chronic interstitial fibrotic disease. During the fibrosis process, myofibroblasts are abnormally activated, collagen is deposited in large quantities and the biomechanical characteristics of lung tissue are significantly altered. In this paper, a systematic review about the changes in lung tissues, cellular biomechanical properties and biomechanical signals during the process of IPF was presented, and the in vitro reproduction of biomechanical features and therapeutic strategies for targeting biomechanics wassummarized, so as to provide references for clinical prevention and treatment of IPF.

Metabonomic Analysis of Wenfei Huaxian Granules Against Idiopathic Pulmonary Fibrosis in Mice / 中国实验方剂学杂志

ObjectiveTo investigate the changes of differential metabolites in the serum of mice at different stages of bleomycin sulfate（BLM）-induced pulmonary fibrosis modeling and administration， and the mechanism of Wenfei Huaxian granules（WHG）against idiopathic pulmonary fibrosis. MethodMice were randomly divided into control group， control group of 14 days， model group， model group of 14 days， low-dose WHG group and high-dose WHG group. BLM（0.04 U per mouse）was injected into the trachea of mice in the model group， model group of 14 days， low-dose WHG group and high-dose WHG group， and sterile normal saline was injected into the trachea of mice in the control group and control group of 14 days. Mice of low-dose WHG group and high-dose WHG group were given different doses of WHG by gavage every day after injection of BLM， and mice of control group， control group of 14 days， model group and model group of 14 days were given sterile water by gavage every day. The peripheral blood of mice in the control group of 14 days and model group of 14 days were taken to prepare serum after injection of BLM for 14 days， and the peripheral blood and other materials of mice in the other groups were taken after continuous administration for 28 days. The bronchoalveolar lavage fluid（BALF）was collected for leucocyte differential count， the pathological examination and hydroxyproline（HYP）content determination of lung tissues of mice were performed， and the small molecule metabolites in serum samples of mice in each group were determined by ultra-high performance liquid chromatography-mass spectrometry（UHPLC-MS）. Principal component analysis（PCA）and orthogonal partial least squares-discriminant analysis（OPLS-DA）were conducted to screen differential metabolites and their biological functions were analyzed. ResultCompared with the control group， a large number of continuous fibrotic foci appeared in the lung tissue of mice in the model group， the alveolitis score， fibrosis degree score and HYP content increased significantly（P<0.01）， and the total number of leukocytes， macrophages and lymphocytes in BALF increased significantly（P<0.05）. A total of 33 differential metabolites were screened between the control group of 14 days and model group of 14 days， mainly lipid metabolites， which were mainly involved in oxidative damage and inflammatory process. A total of 34 differential metabolites， mainly amino acid metabolites， were screened between the control group and model group， mainly involving nucleic acid damage and inflammatory process. Compared with the model group， the HYP content， fibrosis score and alveolitis score in the lung tissue of mice from high-dose WHG group decreased significantly（P<0.05， P<0.01）， and the total number of lymphocytes in BALF decreased significantly（P<0.05）. Compared with the model group， 27， 40 differential metabolites were identified in the serum of mice from the low-dose WHG group and high-dose WHG group separately. There were totally 9 common differential metabolites between the model group and low-dose WHG group/high-dose WHG group， which mainly involved in the metabolic pathways of inflammation related lipids metabolism， arginine and tryptophan metabolism， and the change trends in low-dose WHG group and high-dose WHG group were significantly back-regulated compared with the model group. ConclusionWHG can alleviate BLM-induced pulmonary fibrosis， collagen deposition and inflammatory reaction in mice， and its anti-fibrotic effect may be related to the adjusting of inflammatory factors， nitric oxide and oxidative stress related metabolic pathways.

Antifibrotic therapy in idiopathic pulmonary fibrosis candidates for lung transplantation undergoing pulmonary rehabilitation / Antifibróticos em pacientes com fibrose pulmonar idiopática candidatos a transplante de pulmão e submetidos a reabilitação pulmonar

ABSTRACT Objective: To investigate the impact of pulmonary rehabilitation (PR) on functional outcomes and health-related quality of life (HRQoL) in idiopathic pulmonary fibrosis (IPF) patients placed on a lung transplant waitlist and receiving antifibrotic therapy (AFT). Methods: This was a retrospective observational study of consecutive IPF patients receiving AFT with either pirfenidone or nintedanib (the AFT group) and undergoing PR between January of 2018 and March of 2020. The AFT group and the control group (i.e., IPF patients not receiving AFT) participated in a 12-week PR program consisting of 36 sessions. After having completed the program, the study participants were evaluated for the six-minute walk distance (6MWD) and HRQoL. Pre- and post-PR 6MWD and HRQoL were compared within groups and between groups. Results: There was no significant difference between the AFT and control groups regarding baseline characteristics, including age, airflow limitation, comorbidities, and oxygen requirement. The AFT group had a significant increase in the 6MWD after 12 weeks of PR (effect size, 0.77; p < 0.05), this increase being significant in the between-group comparison as well (effect size, 0.55; p < 0.05). The AFT group showed a significant improvement in the physical component of HRQoL at 12 weeks (effect size, 0.30; p < 0.05). Conclusions: Among IPF patients undergoing PR, those receiving AFT appear to have greater improvements in the 6MWD and the physical component of HRQoL than do those not receiving AFT.

RESUMO Objetivo: Investigar o impacto da reabilitação pulmonar (RP) em desfechos funcionais e na qualidade de vida relacionada à saúde (QVRS) em pacientes com fibrose pulmonar idiopática (FPI) em lista de espera para transplante de pulmão e em tratamento com antifibróticos (AF). Métodos: Estudo observacional retrospectivo com pacientes consecutivos com FPI em tratamento com pirfenidona ou nintedanibe (grupo AF) submetidos a RP entre janeiro de 2018 e março de 2020. O grupo AF e o grupo controle (pacientes com FPI que não estavam em tratamento com AF) participaram de um programa de RP com 36 sessões ao longo de 12 semanas. Após o término do programa, os participantes foram avaliados quanto à distância percorrida no teste de caminhada de seis minutos (DTC6) e à QVRS. A DTC6 e a QVRS pré e pós-RP foram comparadas intra e intergrupos. Resultados: Não houve diferença significativa entre os grupos AF e controle quanto às características basais, incluindo idade, limitação do fluxo aéreo, comorbidades e necessidade de oxigênio. O grupo AF apresentou um aumento significativo da DTC6 após 12 semanas de RP (tamanho do efeito: 0,77; p < 0,05); esse aumento também foi significativo na comparação intergrupos (tamanho do efeito: 0,55; p < 0,05). O grupo AF apresentou melhora significativa no componente físico da QVRS após 12 semanas (tamanho do efeito: 0,30; p < 0,05). Conclusões: Em pacientes com FPI submetidos a RP, a melhora na DTC6 e no componente físico da QVRS parece ser maior naqueles que estejam recebendo tratamento com AF do que naqueles que não o estejam.

Ambulatory oxygen therapy in lung transplantation candidates with idiopathic pulmonary fibrosis referred for pulmonary rehabilitation / Oxigenoterapia ambulatorial em candidatos a transplante de pulmão com fibrose pulmonar idiopática encaminhados para reabilitação pulmonar

ABSTRACT Objective: To determine independent factors related to the use of oxygen and the oxygen flow rate in idiopathic pulmonary fibrosis (IPF) patients placed on a lung transplant waitlist and undergoing pulmonary rehabilitation (PR). Methods: This was a retrospective quasi-experimental study presenting functional capacity and health-related quality of life (HRQoL) data from lung transplant candidates with IPF referred for PR and receiving ambulatory oxygen therapy. The patients were divided into three groups on the basis of the oxygen flow rate: 0 L/min (the control group), 1-3 L/min, and 4-5 L/min. Data on functional capacity were collected by means of the six-minute walk test, and data on HRQoL were collected by means of the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36), being collected before and after 36 sessions of PR including aerobic and strength exercises. Results: The six-minute walk distance improved in all three groups (0 L/min: Δ 61 m, p < 0.001; 1-3 L/min: Δ 58 m, p = 0.014; and 4-5 L/min: Δ 35 m, p = 0.031). Regarding HRQoL, SF-36 physical functioning domain scores improved in all three groups, and the groups of patients receiving ambulatory oxygen therapy had improvements in other SF-36 domains, including role-physical (1-3 L/min: p = 0.016; 4-5 L/min: p = 0.040), general health (4-5 L/min: p = 0.013), social functioning (1-3 L/min: p = 0.044), and mental health (1-3 L/min: p = 0.046). Conclusions: The use of ambulatory oxygen therapy during PR in lung transplant candidates with IPF and significant hypoxemia on exertion appears to improve functional capacity and HRQoL.

RESUMO Objetivo: Determinar fatores independentes relacionados ao uso de oxigênio e ao fluxo de oxigênio em pacientes com fibrose pulmonar idiopática (FPI) em lista de espera para transplante de pulmão e em reabilitação pulmonar (RP). Métodos: Estudo quase experimental retrospectivo no qual são apresentados dados referentes à capacidade funcional e qualidade de vida relacionada à saúde (QVRS) de pacientes com FPI candidatos a transplante de pulmão e encaminhados para RP em oxigenoterapia ambulatorial. Os pacientes foram divididos em três grupos com base no fluxo de oxigênio: 0 L/min (grupo controle), 1-3 L/min e 4-5 L/min. Os dados referentes à capacidade funcional foram coletados por meio do teste de caminhada de seis minutos, e os dados referentes à QVRS foram coletados por meio do Medical Outcomes Study 36-item Short-Form Health Survey (SF-36), sendo coletados antes e depois de 36 sessões de RP com exercícios aeróbicos e de força. Resultados: A distância percorrida no teste de caminhada de seis minutos melhorou nos três grupos (0 L/min: Δ 61 m, p < 0,001; 1-3 L/min: Δ 58 m, p = 0,014; 4-5 L/min: Δ 35 m, p = 0,031). No tocante à QVRS, a pontuação obtida no domínio "capacidade funcional" do SF-36 melhorou nos três grupos, e os pacientes que receberam oxigenoterapia ambulatorial apresentaram melhora em outros domínios do SF-36: função física (1-3 L/min: p = 0,016; 4-5 L/min: p = 0,040), estado geral de saúde (4-5 L/min: p = 0,013), aspectos sociais (1-3 L/min: p = 0,044) e saúde mental (1-3 L /min: p = 0,046). Conclusões: O uso de oxigenoterapia ambulatorial durante a RP em candidatos a transplante de pulmão com FPI e hipoxemia significativa aos esforços parece melhorar a capacidade funcional e a QVRS.

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.

Idiopathic pulmonary fibrosis: current diagnosis and treatment / Fibrose pulmonar idiopática: diagnóstico e tratamento atuais

ABSTRACT Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disease without a clear recognizable cause. IPF has been at the forefront of new diagnostic algorithms and treatment developments that led to a shift in patients' care in the past decade, indeed influencing the management of fibrotic interstitial lung diseases other than IPF itself. Clinical presentation, pathophysiology, and diagnostic criteria are briefly addressed in this review article. Additionally, evidence regarding the use of antifibrotics beyond the settings of clinical trials, impact of comorbidities, and therapeutic approaches other than pharmacological treatments are discussed in further detail.

RESUMO A fibrose pulmonar idiopática (FPI) é uma doença pulmonar crônica devastadora sem uma causa claramente reconhecida, que está na vanguarda de novos algoritmos de diagnóstico e do desenvolvimento de tratamentos que levaram a uma mudança no cuidado desses pacientes na última década, influenciando de fato o manejo de doenças pulmonares intersticiais fibróticas além da própria FPI. A apresentação clínica, a fisiopatologia e os critérios diagnósticos são brevemente abordados neste artigo de revisão. Além disso, as evidências sobre o uso de antifibróticos além dos cenários de ensaios clínicos, o impacto de comorbidades e abordagens terapêuticas, além dos tratamentos farmacológicos são discutidos detalhadamente.

Effect on the Prevalence of Various Diffuse Parenchymal Lung Diseases due to Paradigm Change in the Guidelines

Background: Diffuse parenchymal lung diseases (DPLDs) have gone through various changes in nomenclature and classification since they were first described in 1868. Increasing knowledge about their etiopathogenesis has since led to several reclassifications and changes in the nomenclature. This has had a major impact on the prevalence of each interstitial lung disease (ILD) reported by the different registries worldwide. In this study, we attempted to describe the distribution of the different DPLDs in our population and reported changes in prevalence due to changing diagnostic criteria for the disease. Materials and methods: We analyzed retrospective data of 434 patients. For the initial 75 patients, ATS/ERS guidelines published in 2002 were followed in the diagnosis of the ILD (group I). In the later part of the study (359 patients), the diagnosis was based on the computed tomography (CT) patterns defined by ATS/ERS/JPS/ALAT statement on diagnosis of idiopathic pulmonary fibrosis (IPF) and updated 2013 ATS/ERS guidelines (group II). Results: Of the 75 patients in group I, IPF was the most common diagnosis (52%) made at that time, followed by sarcoidosis and connective tissue-related ILD (CTD-ILD) with 12% each. Group II had 359 patients, with IPF again being the most commonly diagnosed ILD with 21.3%. This was followed by CTD-ILD (18.6%), sarcoid (14.7%), and idiopathic nonspecific interstitial pneumonitis (iNSIP; 13.3%). The changing guidelines have an impact on reporting of different DPLD by our multidisciplinary teamover a period of time. Though IPF was the most commonest DPLD reported among both the groups, the diagnosis of IPF had fallen by more than half in the second group. It was paralleled by an increase in the diagnosis of iNSIP and chronic hypersensitivity pneumonitis. These reported changes in the prevalence of DPLDs may reflect the better-defined criteria in the latest guidelines and a better understanding of the fibrotic ILDs other than IPF by the multidisciplinary team. Conclusions: The frequency of diagnosis of the different DPLDs has changed, following the publication of several guidelines in the last decade. It has recognized newer entities with greater clarity, such as idiopathic NSIP and interstitial pneumonia with autoimmune features.

Caracterización clínica de pacientes con fibrosis pulmonar idiopática en un hospital de tercer nivel en la ciudad de Quito-Ecuador / Clinical Characterization of patients with Idiopathic Pulmonary Fibrosis in a Tertiary Hospital of the City of Quito-Ecuador

RESUMEN Introducción: La fibrosis pulmonar idiopática es una enfermedad progresiva y fa tal caracterizada por el hallazgo de neumonía intersticial usual en tomografía de alta resolución o biopsia pulmonar, o en discusión multidisciplinar y el descarte de otras etiologías como enfermedades del tejido conectivo o exposicionales. En cuanto a los objetivos de este trabajo, consisten en conocer las características clí nicas, la función pulmonar y la supervivencia del grupo de pacientes con diagnóstico de fibrosis pulmonar idiopática evaluados en la clínica de intersticiales del Hospital Carlos Andrade Marín. Material y métodos: Se trata de un estudio transversal, retrospectivo, observacional. La población de estudio la constituyeron los pacientes con diagnóstico de fibrosis pul monar idiopática atendidos en la clínica de intersticiales del Hospital Carlos Andrade Marín entre enero del 2018 y febrero del 2020. Resultados: De 35 pacientes con fibrosis pulmonar idiopática incluidos para el análi sis, el 85,7% fueron del sexo masculino. Al momento del diagnóstico, la edad pro medio fue de 69,7 años (DE: 9,26, Rango: 38-87 años). El 20% y 37,1% presentaron disnea de grado 3 y grado 4, respectivamente. El 60% presentaron antecedentes de tabaquismo. El 45,7% de los diagnósticos se hicieron tanto con evaluación clínica multidisciplinaria y tomografía axial computarizada de alta resolución. Conclusiones: Hemos informado la mayor cohorte de fibrosis pulmonar idiopática en el Ecuador, nuestros resultados han identificado poblaciones similares con otros gru pos de estudio en los que la tomografía computarizada de alta resolución y el análisis multidisciplinar son los métodos más utilizados en el diagnóstico.

ABSTRACT Background: idiopathic pulmonary fibrosis is a progressive, fatal disease character ized by the findings of usual interstitial pneumonia in a high resolution tomography or lung biopsy, or in a multidisciplinary discussion, also discarding other etiologies such as connective tissue diseases or diseases associated with toxic exposure. The objective of this work was to know the clinical characteristics, lung function and survival of the group of patients diagnosed with idiopathic pulmonary fibrosis who were evaluated at the Interstitial Lung Disease Clinic of the Hospital Carlos Andrade Marín. Methods: retrospective, cross-sectional, observational study. The study population consisted of patients diagnosed with idiopathic pulmonary fibrosis who had been treat ed at the Interstitial Lung Disease Clinic of the Hospital Carlos Andrade Marín between January, 2018 and February, 2020. Results: 85.7% of the 35 patients with idiopathic pulmonary fibrosis included in the analysis were male. At the time of the diagnosis, the mean age was 69.7 years (SD [standard deviation]: 9.26, range: 38-87 years). 20% and 37.1% of patients showed dyspnea grade 3 and 4, respectively. 60% had smoking history. 45.7% of the diagnoses were made with a multidisciplinary clinical evaluation and high resolution computed axial tomography. Conclusions: we have reported the largest cohort of patients with idiopathic pulmo nary fibrosis in Ecuador; our results identified similar populations with other study groups where the high resolution computed tomography and multidisciplinary analysis are the most used methods for the diagnosis.

Seguimiento de 20 pacientes portadores de fibrosis pulmonar idiopática tratados con nintedanib / Follow-up of 20 patients with idiopathic pulmonary fibrosis treated with nintedanib

Se presenta un estudio observacional compasivo de seguimiento de 20 pacientes portadores de Fibrosis Pulmonar Idiopática tratados con Nintedanib, que muestra que Nintedanib es un medicamento en general bien tolerado, sin efectos adversos serios, que otorga una sobrevida más prolongada que la que cabría esperar en pacientes con esta enfermedad.

A compassionate observational follow-up study of 20 patients with Idiopathic Pulmonary Fibrosis treated with Nintedanib is presented, showing that Nintedanib is a generally well-tolerated drug, with no serious adverse effects, that grants a longer survival in real-life patients.

Tratamiento de fibrosis pulmonar idiopática con células madre adultas autólogas de médula ósea / Treatment of idiopathic pulmonary fibrosis with autologous adult bone marrow stem cells

Introducción: La fibrosis pulmonar idiopática representa una enfermedad degenerativa con pronóstico nefasto, cuyas opciones terapéuticas son muy limitadas, por lo que es necesario evaluar alternativas asequibles a la población. Objetivo: Evaluar el tratamiento con células madre adultas autólogas de médula ósea de paciente de 68 años con diagnóstico radiológico de fibrosis pulmonar y disnea en reposo. Presentación del caso: La paciente acudió a consulta con disnea en reposo y saturación digital de 74 por ciento, la cual después de su primer tratamiento endovenoso con células madre adultas de médula ósea, logró una mejoría significativa con saturaciones que oscilaron entre 85 y 90 por ciento, a los 4 meses de la primera terapia. A los 8 meses de la primera sesión recibió una segunda dosis, con la cual subió la saturación a valores entre 94 y 97 por ciento, a las tres semanas de ésta última. Conclusión: El tratamiento con células madre adultas autólogas de médula ósea podría mejorar los signos y síntomas de los pacientes con fibrosis pulmonar idiopática(AU)

Introduction: Idiopathic pulmonary fibrosis represents a degenerative disease with a dire prognosis, whose therapeutic options are very limited, so it is necessary to evaluate alternatives available to the population. Objective: To evaluate treatment with autologous adult bone marrow (BM) stem cells in a 68-year-old patient with a radiological diagnosis of pulmonary fibrosis and dyspnea at rest. Case presentation: The patient attended the consultation with dyspnea at rest, and digital saturation of 74 percent, which after her first intravenous treatment with adult bone marrow stem cells, achieved significant improvement, with saturations ranging between 85 and 90 percent at 4 months after the first therapy. Eight months after the first session, she received a second dose, with which she increased the saturation to values between 94 and 97 percent, three weeks after the latter. Conclusion: Conclusion: Treatment with autologous adult bone marrow stem cells could improve the signs and symptoms of patients with idiopathic pulmonary fibrosis(AU)

Impacto clínico de un grupo de discusión multidisciplinaria en el diagnóstico de fibrosis pulmonar idiopática en Colombia / Clinical impact of a multidisciplinary discussion group on the diagnosis of idiopathic pulmonary fibrosis in Colombia

Resumen Introducción: la fibrosis pulmonar idiopática (FPI) es una enfermedad pulmonar intersticial (EPID) de mal pronóstico, considerada huérfana en Colombia. Un diagnóstico correcto tiene implicaciones para el paciente y los costos de atención. Los grupos de discusión multidisciplinaria (GDM) se consideran el estándar de oro en el diagnóstico. No hay estudios previos en Colombia de la experiencia de un GDM. Objetivos: evaluar el impacto de un GDM en una institución de cuarto nivel en Bogotá en cambio de diagnóstico de pacientes con EPID y la concordancia entre el diagnóstico inicial y final de FPI. Material y métodos: pacientes con EPID evaluados entre 2015-2018 por el GDM conformado por neumólogos, radiólogo, patólogo y reumatólogos. Criterios ATS/ERS/JRS/ALAT de diagnóstico de FPI. Descripción del cambio en el diagnóstico y concordancia entre el diagnóstico inicial y del GDM en FPI. Resultados: de 165 pacientes con EPID se cambió el diagnóstico en 35.2%. En 77.3% pacientes con diagnóstico inicial de FPI y en 6.7% con diagnóstico inicial diferente a FPI el GDM confirmó FPI. Al descartar FPI, los principales diagnósticos fueron neumonitis de hipersensibilidad en fase crónica (29.4%) y neumonía intersticial no específica (23.5%). El índice kappa entre el diagnóstico inicial y final de FPI fue 0.71 (0.60-0.82). Conclusiones: el GDM en EPID tuvo un importante impacto clínico demostrado por un alto porcentaje de cambió del diagnóstico de remisión. Se descartó el diagnóstico inicial de FPI en un porcentaje significativo de pacientes y se ratificó en un grupo menor sin esta sospecha clínica inicial. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2017).

Abstract Introduction: idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease (ILD) with a poor prognosis, considered an orphan disease in Colombia. An accurate diagnosis has implications for the patient and healthcare costs. Multidisciplinary discussion groups (MDGs) are considered the gold standard for diagnosis. There are no prior studies in Colombia on the experience of an MDG. Objectives: to evaluate the impact of an MDG in a quaternary care institution in Bogotá on the change in the diagnosis of patients with ILD and the concordance between the initial and final diagnosis of IPF. Materials and methods: patents with ILD evaluated from 2015-2018 by the MDG made up of pulmonologists, a radiologist, a pathologist and rheumatologists. The ATS/ERS/JRS/ALAT diagnostic criteria for IPF. A description of changes in the diagnosis and the agreement between the initial diagnosis and the MDG diagnosis of IPF. Results: out of 165 patients with ILD, the diagnosis was changed in 32.5%. The MDG confirmed IPF in 77.3% of patients with an initial diagnosis of ILD and 6.7% of those with a different initial diagnosis. When IPF was ruled out, the main diagnoses were chronic hypersensitivity pneumonitis (24.8%) and nonspecific interstitial pneumonia (23.5%). The Kappa index between the initial and final IPF diagnoses was 0.71 (0.60-0.82). Conclusions: the MDG on ILD had a significant clinical impact evidenced by a high percentage of change in the referral diagnosis. The initial diagnosis of IPF was ruled out in a significant percentage of patients and confirmed in a smaller group which did not have this initial clinical suspicion. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2017).

Interobserver agreement regarding the Fleischner Society diagnostic criteria for usual interstitial pneumonia patterns on computed tomography / Concordância interobservador nas categorias diagnósticas de pneumonia intersticial usual propostas pela Fleischner Society na tomografia computadorizada

Abstract Objective: To assess interobserver agreement among radiologists regarding the current Fleischner Society diagnostic criteria for usual interstitial pneumonia (UIP) patterns on computed tomography (CT). Materials and Methods: Using the Fleischner Society criteria for UIP CT patterns, five raters, working independently, categorized the high-resolution CT (HRCT) scans of 44 patients with interstitial lung disease who underwent lung biopsy. The raters also evaluated the presence, extent, and distribution of the most relevant imaging findings, as well as indicating their level of confidence in the most likely diagnosis and in up to three diagnostic hypotheses. Results: There was moderate to substantial interobserver agreement regarding the UIP patterns on HRCT—kappa statistic (κ) = 0.59-0.61. Interobserver agreement for the binary scores was substantial (κ = 0.77-0.79), whereas that for the presence of honeycombing was almost perfect (κ = 0.81-0.96). There was agreement regarding at least one of the three diagnostic hypotheses in only 36.4% of the cases. For the level of confidence in the most likely diagnosis, there was only slight to fair agreement (κ = 0.19-0.21). Conclusion: Interobserver agreement regarding the current Fleischner Society CT criteria for UIP was moderate to substantial among raters with varying levels of experience. There was only slight to fair agreement regarding the diagnostic hypotheses and for the level of confidence in the most likely diagnosis.

Resumo Objetivo: Avaliar a concordância interobservador entre radiologistas para os critérios atuais da Fleischner Society para categorias diagnósticas de pneumonia intersticial usual (PIU) em tomografia computadorizada (TC). Materiais e Métodos: Cinco observadores categorizaram independentemente as imagens de TC de 44 pacientes com doença pulmonar intersticial que foram submetidos a biópsia pulmonar empregando as últimas categorias de diagnóstico da Sociedade Fleischner para UIP. Também foram avaliadas presença, extensão e distribuição dos achados de imagem mais relevantes, bem como a confiança no diagnóstico mais provável e em até três hipóteses diagnósticas. Resultados: Houve concordância moderada a alta para as categorias diagnósticas entre os observadores (κ = 0,59-0,61). A concordância interobservador para a pontuação binária foi alta (κ = 0,77-0,79), enquanto para a presença de faveolamento foi considerada de alta a muito alta (κ = 0,81-0,96). Houve concordância em uma das três hipóteses diagnósticas em apenas 36,4% dos casos. Baixa concordância foi encontrada para o diagnóstico mais provável (κ = 0,19-0,21). Conclusão: A concordância entre observadores para os critérios atuais de TC da Fleischner Society para UIP foi moderada a alta entre observadores com diferentes níveis de experiência. Houve baixa concordância nas hipóteses diagnósticas e quanto ao grau de confiança no diagnóstico primário.