"Interstitial lung abnormalities": translation to and use in Portuguese / Anormalidades pulmonares intersticiais: tradução e uso na língua portuguesa

Abstract Objective: To conduct a survey on the use of the term "interstitial lung abnormalities" in radiology reports in Brazil, propose an appropriate Portuguese-language translation for the term, and provide a brief review of the literature on the topic. Materials and Methods: A survey was sent via electronic message to various radiologists in Brazil, asking about their familiarity with the term, which translation of the term they use in Portuguese, and whether they use the criteria proposed by the Fleischner Society. Results: A total of 163 responses were received, from all regions of Brazil. Although the vast majority (88%) of the respondents stated that they were familiar with the term "interstitial lung abnormalities", there was considerable variation regarding the equivalent term they used in Portuguese. Conclusion: We suggest that the term "anormalidades pulmonares intersticiais" be used in order to standardize radiology reports and disseminate knowledge of these findings in Brazil.

Resumo Objetivo: Fazer um levantamento sobre o uso do termo interstitial lung abnormalities nos laudos radiológicos no Brasil, propor uma tradução para o termo e fazer uma breve revisão sobre o tema. Materiais e Métodos: Foi enviada uma pesquisa, por meio de mensagem eletrônica, para diversos radiologistas de todo o Brasil, questionando sobre a familiarização com o termo, qual tradução em português utilizam e se usam os critérios propostos pela diretriz da Sociedade Fleischner. Resultados: Foram recebidas 163 respostas de todas as regiões do Brasil e a grande maioria dos radiologistas respondeu estar familiarizado com o termo interstitial lung abnormalities (88%), mas houve grande variação em relação ao termo utilizado como tradução para o português. Conclusão: Sugerimos a padronização do termo "anormalidades pulmonares intersticiais", a fim de uniformizar os relatórios radiológicos e difundir esta entidade no País.

Riesgo cardiovascular en pacientes con esclerosis sistémica / Cardiovascular Risk in Patients with Systemic Sclerosis

Introducción: El riesgo cardiovascular es importante en la evaluación de los pacientes con esclerosis sistémica. Objetivo: Determinar el riesgo cardiovascular en pacientes con esclerosis sistémica. Métodos: Se realizó un estudio transversal y descriptivo en pacientes protocolizados del Servicio de Reumatología, en el período de enero 2020 a enero 2022. Se recogieron variables demográficas, clínicas, y se aplicó la calculadora de riesgo cardiovascular Framingham. Resultados: Se incluyeron 105 pacientes con edad media de 48,6 ± 15,3 años, el grupo más frecuente de 50 a 59 años (36,2 por ciento), predominó el sexo femenino 92,2 por ciento el color de piel blanca (74,3 por ciento), el tiempo de evolución fue mayor a 5 años (66,7 por ciento) con una media de 10,5 ± 9,3. El valor promedio de la escala de gravedad modificada de Medsger fue 5,1 ± 2,7 y el 72,4 por ciento con afectación leve. El fenómeno de Raynaud y la fibrosis pulmonar fueron más frecuentes con un 89,5 por ciento y 55,2 por ciento. El índice de Rodnan en promedio fue de 13,1 ± 8,0 y los reactantes de fase aguda normales en la mayoría. Los factores de riesgo cardiovascular más frecuentes fueron la HTA (30,2 por ciento) y dislipidemia (19,9 por ciento). El índice de masa corporal que predominó fue de peso adecuado (54,3 por ciento). Predominó el riesgo cardiovascular bajo según score de Framingham (86 por ciento). Existieron diferencias significativas entre las medias del tiempo de evolución y el riesgo cardiovascular (10 ± 6,9 frente a 9,6 ± 8,8 frente a 16,9 ± 10,8; p = 0,032). Conclusiones: El riesgo cardiovascular en los pacientes con esclerosis sistémica fue bajo(AU)

Introduction: Cardiovascular risk is important in the evaluation of patients with systemic sclerosis. Objective: To determine the cardiovascular risk in patients with systemic sclerosis. Methods: A cross-sectional and descriptive study was carried out in protocolized patients of Rheumatology Service, from January 2020 to January 2022. Demographic and clinical variables were collected, and Framingham cardiovascular risk calculator was used. Results: One hundred five patients were included with a mean age of 48.6 ± 15.3 years, the most frequent group was 50 to 59 years (36.2percent), female sex (92.2percent) predominated, as well as white skin color (74.3percent). The evolution time was greater than 5 years (66.7percent) with a mean of 10.5 ± 9.3. The average value of modified Medsger severity scale was 5.1 ± 2.7 and 72.4percent had mild involvement. Raynaud's phenomenon and pulmonary fibrosis were more common at 89.5percent and 55.2percent. Rodnan index on average was 13.1 ± 8.0 and the acute phase reactants were normal in the majority. The most frequent cardiovascular risk factors were HBP (30.2percent) and dyslipidemia (19.9percent). The predominant body mass index was adequate weight (54.3percent). Low cardiovascular risk according to Framingham score prevailed (86percent). There were significant differences between the mean duration of evolution and cardiovascular risk (10 ± 6.9 vs. 9.6 ± 8.8 vs. 16.9 ± 10.8; p = 0.032). Conclusions: The cardiovascular risk in patients with systemic sclerosis was low(AU)

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.

Pathogenesis of Idiopathic Pulmonary Fibrosis and Modulating Effect of Chinese Medicine： A Review / 中国实验方剂学杂志

Idiopathic pulmonary fibrosis （IPF）， as a progressive lung disease， has a poor prognosis and no reliable and effective therapies. IPF is mainly treated by organ transplantation and administration of chemical drugs， which are ineffective and induce side effects， failing to meet the clinical needs. Therefore， developing safer and more effective drugs has become an urgent task， which necessitates clear understanding of the pathogenesis of IPF. The available studies about the pathogenesis of IPF mainly focus on macrophage polarization， epithelial-mesenchymal transition （EMT）， oxidative stress， and autophagy， while few studies systematically explain the principles and links of the pathogeneses. According to the traditional Chinese medicine theory， Qi deficiency and blood stasis and Qi-Yang deficiency are the key pathogeneses of IPF. Therefore， the Chinese medicines or compound prescriptions with the effects of replenishing Qi and activating blood， warming Yang and tonifying Qi， and eliminating stasis and resolving phlegm are often used to treat IPF. Modern pharmacological studies have shown that such medicines play a positive role in inhibiting macrophage polarization， restoring redox balance， inhibiting EMT， and regulating cell autophagy. However， few studies report how Chinese medicines regulate the pathways in the treatment of IPF. By reviewing the latest articles in this field， we elaborate on the pathogenesis of IPF and provide a comprehensive overview of the mechanism of the active ingredients or compound prescriptions of Chinese medicines in regulating IPF. Combining the pathogenesis of IPF with the modulating effects of Chinese medicines， we focus on exploring systemic treatment options for IPF， with a view to providing new ideas for the in-depth study of IPF and the research and development of related drugs.

Correlation between lung allocation score and early death risk of patients with idiopathic pulmonary fibrosis after lung transplantation / 器官移植

Objective To analyze the correlation between the lung allocation score (LAS) and the risk of early death and complications in patients with idiopathic pulmonary fibrosis (IPF) after lung transplantation. Methods Clinical data of 275 patients with IPF were retrospectively analyzed. The correlation between LAS and the risk of early death in IPF patients after lung transplantation and the correlation between LAS and complications at postoperative 1 year was assessed by univariate and multivariate Cox regression analyses. Results Among 275 recipients, 62, 83, 95 and 108 cases died within postoperative 30, 90, 180 and 365 d, respectively. LAS was correlated with 30-, 90-, 180- and 365-d fatality of IPF patients (all P<0.05), whereas it was not correlated with the incidence of primary graft dysfunction (PGD) and acute kidney injury (AKI) at 365 d after lung transplantation (both P>0.05). Conclusions LAS is correlated with the risk of early death of IPF patients after lung transplantation. While, it is not correlated the incidence of PGD and AKI early after lung transplantation. Special attention should be paid to the effect of comprehensive factors upon PGD and AKI.

Mechanism of Medicated Serum of Buyang Huanwutang in Inhibiting Endothelial-to-mesenchymal Transition of Human Pulmonary Artery Endothelial Cells Based on Wnt1/β-catenin Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the role of the Wnt1/β-catenin signaling pathway in the intervention of medicated serum of Buyang Huanwutang （BYHWT） in endothelial-to-mesenchymal transition （EndMT） of human pulmonary artery endothelial cells （HPAECs） as well as its related mechanisms. MethodMedicated serum of BYHWT was prepared by gavage to New Zealand rabbits with a dosage of 53.36 g·kg-1·d-1 after decocting the medicine as usual. In addition， the same volume of normal saline was used to prepare blank serum. The HPAECs were cultured in vitro， and then induced by the transforming growth factor-β1 （TGF-β1） to establish the EndMT model. Five groups were established： blank group （10% blank serum）， model group （TGF-β1+10% blank serum）， low-dose BYHWT group （TGF-β1+2.5% medicated serum+7.5% blank serum）， medium-dose BYHWT group （TGF-β1+5% medicated serum+5% blank serum） and high-dose BYHWT group （TGF-β1+10% medicated serum）. Through Western blot， the expressions of Wnt1， β-catenin， and glycogen synthase kinase-3β （GSK-3β） were detected. In order to further clarify the mechanism of the Wnt1/β-catenin signaling pathway in the intervention of the medicated serum of BYHWT in inhibiting EndMT， the overexpression of β-catenin was confirmed by polymerase chain reaction after plasmid of overexpression β-catenin was constructed and transfected into the HPAECs. The HPAECs were intervened by 10% medicated serum with the optimal effect in previous studies. Then， they were divided into another five groups： the blank group （10% blank serum）， the model group （TGF-β1+10% blank serum）， the BYHWT group （TGF-β1+10% medicated serum）， the BYHWT+overexpression plasmid control group （TGF-β1+10% medicated serum+blank plasmid） and the BYHWT+β-catenin overexpression plasmid group （TGF-β1+10% medicated serum+β-catenin）. Apart from that， cell proliferation ability was detected by the methyl thiazolyl tetrazolium （MTT） method and cell migration ability by scratch assay and Transwell assay together. Immunofluorescence was adopted to detect the expressions of platelet endothelial cell adhesion molecule （PECAM-1/CD31）， vascular endothelial cadherin （VE-cadherin）， fibroblast-specific protein 1 （FSP1）， and α-smooth muscle actin （α-SMA）. ResultIn comparison to the blank group， the expressions of Wnt1 and β-catenin were significantly increased （P<0.01） while the expression of GSK-3β significantly decreased （P<0.01） in the model group. In comparison to the model group， the expressions of Wnt1 and β-catenin were significantly decreased （P<0.01） while the expression of GSK-3β was significantly increased （P<0.01） in the high-dose BYHWT group. The expression of β-catenin was significantly decreased （P<0.01） while the expression of GSK-3β was significantly increased （P<0.01） in the medium-dose BYHWT group. There was no significant difference in these indexes of the low-dose BYHWT group. In comparison to the blank group， proliferation and migration abilities were remarkably increased （P<0.01） and the immunofluorescence intensities of CD31 and VE-cadherin were decreased， while those of FSP1 and α-SMA were increased in the model group. In comparison to the model group， proliferation and migration abilities were significantly decreased （P<0.01） and the immunofluorescence intensities of CD31 and VE-cadherin were increased， while those of FSP1 and α-SMA diminished in the BYHWT group. Beyond that， the change trend of those indexes in the BYHWT+β-catenin overexpression plasmid group was consistent with that in the model group. In comparison to the BYHWT+overexpression plasmid control group， proliferation and migration abilities were significantly increased （P<0.01） and the immunofluorescence intensities of CD31 and VE-cadherin were decreased， while those of FSP1 and α-SMA were increased in the BYHWT+β-catenin overexpression plasmid group. ConclusionMedicated serum of BYHWT can inhibit EndMT of HPAECs by the Wnt1/β-catenin signaling pathway.

Lung transplantation after paraquat poisoning in an adolescent: one case report and literature review / 器官移植

Objective To summarize the effect of the timing of lung transplantation and related treatment measures on clinical prognosis of patients with paraquat poisoning. Methods Clinical data of a patient with paraquat poisoning undergoing bilateral lung transplantation were retrospectively analyzed. Clinical manifestations, auxiliary examination, diagnosis and treatment of this patient were summarized and analyzed. Results A 17-year-old adolescent was admitted to hospital due to nausea, vomiting, cough and systemic fatigue after oral intake of 20-30 mL of 25% paraquat. After symptomatic support treatment, the oxygen saturation was not improved, and pulmonary fibrosis continued to progress. Therefore, sequential bilateral lung transplantation was performed under extracorporeal membrane oxygenation (ECMO). After postoperative rehabilitation and active prevention and treatment for postoperative complications, the patient was discharged at postoperative 50 d. Conclusions The timing of lung transplantation after paraquat poisoning may be selected when the liver and kidney function start to recover. Active and targeted prevention of potential pathogen infection in perioperative period and early rehabilitation training contribute to improving clinical prognosis of lung transplant recipients.

AA Amyloidosis Secondary to Horton's Disease Complicated by Pulmonary Fibrosis: A Very Challenging Diagnosis and Therapy

AA amyloidosis is a classic and serious complication of many chronic inflammatory processes, whether of infectious, autoimmune, or neoplastic origin. It is frequently complicated by kidney damage, often in the form of a nephrotic syndrome. Giant cell arteritis is a common inflammatory arteritis in the elderly; however, it rarely causes AA amyloidosis. We report a rare case of Horton disease causing AA amyloidosis in an elderly patient with history of myopericarditis and repeated episodes of congestive heart failure. Patient was treated initially with dual therapy based on corticosteroids and anti TNF therapy (Tocilizumab) associated with heart failure therapy recommended by the European society of cardiology (ESC 2021 guidelines on Heart Failure). The initial outcome was favorable but later complicated by the involvement of the lungs; pulmonary fibrosis, responsible for repeated episodes of pleural effusion non controlled in spite of high dose of loop diuretics and repeated pleural punction. Patient died shortly after her second hospitalization due to respiratory insufficiency.

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.

A review on post-COVID-19 pulmonary fibrosis and the role of nintedanib in its management

Pulmonary fibrosis as a complication of COVID-19 has been widely reported. Several studies have reported prolonged respiratory symptoms in significant numbers of people lasting months after the acute episode of COVID-19 infection. Nintedanib is being explored as a potential therapeutic agent in the treatment of post-COVID-19 pulmonary fibrosis. However, the exact role of nintedanib in the treatment of post-COVID-19 pulmonary fibrosis is not clear. Objectives of this article are to perform a scoping review of the literature on the mechanism of pulmonary fibrosis, role of nintedanib in the treatment of post-COVID-19 pulmonary fibrosis, and emerging treatments in the treatment of post-COVID-19 pulmonary fibrosis. The United States Clinical Trials Registry and Clinical Trials Registry of India were searched to identify studies evaluating the role of nintedanib in post-COVID-19 pulmonary fibrosis. Embase and PubMed databases were searched and relevant articles were reviewed. Over all 26 article in PubMed and 67 articles in Embase were reviewed. There are several ongoing studies evaluating the safety and efficacy of nintedanib in the treatment of post-COVID-19 pulmonary fibrosis. Some studies have shown promising results for nintedanib while results from several large ongoing clinical trials are awaited. Use of nintedanib in post-COVID-19 pulmonary fibrosis is promising based on the preliminary evidence from the present studies. However, the current evidence is limited and more evidence is awaited from the ongoing randomized clinical trials evaluating the safety and efficacy of nintedanib in the management of post-COVID-19 pulmonary fibrosis.

Effects of N-butanol extract of Amygdalus mongolica on rats with bleomycin‐induced pulmonary fibrosis based on metabolomics

Pulmonary fibrosis (PF) is a major public health issue with limited treatment options. As the active ingredient of the n-butanol extract of Amygdalus mongolica (BUT), amygdalin inhibits PF. However, its mechanisms of action are unclear and need further verification. Therefore, the purpose of the present studies was to investigate the anti-fibrotic effects of BUT on PF by serum metabolomics and the transforming growth factor β (TGF-β) pathway. Sixty male Sprague-Dawley rats were randomly divided into control, untreated PF, prednisone-treated (5 mg/kg), and BUT-treated (1.75, 1.25, 0.75 g/kg) groups, and the respective drugs were administered intragastrically for 21 days. The serum metabolomics profiles were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) and metabolism network analysis. The expression of TGF-β1, Smad-3, Smad-7, and α-smooth muscle actin (α-SMA) was measured using a real-time polymerase chain reaction in the lung tissue. BUT significantly alleviated fibrosis by reducing the mRNA expressions of TGF-β1 (from 1.73 to 1.13), Smad-3 (from 2.01 to 1.19), and α-SMA (from 2.14 to 1.19) and increasing that of Smad7 (from 0.17 to 0.62). Twenty-eight potential biomarkers associated with PF were identified. In addition, four key biomarkers were restored to baseline levels following BUT treatment, with the lowest dose showing optimal effect. Furthermore, A. mongolica BUT was found to improve PF by the pentose phosphate pathway and by taurine, hypotaurine, and arachidonic acid metabolism. These findings revealed the mechanism of A. mongolica BUT antifibrotic effects and metabolic activity in PF rats and provided the experimental basis for its clinical application.

Fibroelastosis pleuroparenquimatosa e hipertension pulmonar: un fenotipo diferente?

La fibroelastosis pleuroparenquimatosa es una enfermedad pulmonar inusual con características clínicas, radiológicas y patológicas únicas, que se ha incluido recientemente en el consenso actualizado sobre neumonías intersticiales idiopáticas. Su nombre hace referencia a una combinación de fibrosis que involucra la pleura visceral y cambios fibroelastóticos que predominan en el parénquima pulmonar subpleural. Aunque se han descrito varias asociaciones de enfermedades, no se ha identificado de manera inequívoca ninguna causa única. El diagnóstico se sustenta en criterios clínicos-radiológicos y de hallazgos histopatológicos cuando se dispone de biopsias. Son escasos los reportes sobre la asociación entre esta entidad y la hipertensión pulmonar. No existe tratamiento hasta la fecha, aunque se relatan sucesos en algunos casos de transplante pulmonar. Describimos las características clínicas de un paciente atendido en un hospital del Paraguay.

Pleuroparenchymal fibroelastosis is an unusual lung disease with unique clinical, radiological, and pathological characteristics that has recently been included in the updated consensus on idiopathic interstitial pneumonia. Their name refers to a combination of fibrosis involving the visceral pleura and fibro-elastic changes that predominate in the subpleural pulmonary parenchyma. Although several associations between diseases have been described, no single cause has been unequivocally identified. The diagnosis is based on clinical-radiological criteria and histopathological findings when biopsies are available. There are few reports on the association between this entity and pulmonary hypertension. There is no treatment to date, although some cases of lung transplantation have been successful. We describe the clinical characteristics of a patient treated in a hospital in Paraguay.

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.

Research progress on anti-pulmonary fibrosis effect and mechanism of flavonoids / 中国药房

Pulmonary fibrosis is the end-stage manifestation of a large class of lung diseases characterized by fibroblast proliferation and accumulation of a large amount of extracellular matrix accompanied by inflammatory injury and tissue structure destruction. Studies have shown that flavonoids have anti-pulmonary fibrosis effects through multiple paths， including dihydromyricetin， morin and fisetin can inhibit fibroblast differentiation； Trollius altaicus flavonoids， hesperidin and linarin can play an anti-inflammatory role； total flavonoids from Scutellaria baicalensis， scutellarin and chrysin can inhibit epithelial- mesenchymal transition； total flavonoids of Litchi chinensis， diosmin and silybin can play an anti-oxidative stress role； quercetin， baicalin and apigenin can regulate autophagy； total flavonoids of Oxytropis falcata， calycosin and dihydroquercetin can regulate apoptosis； naringin， scutellarin and total flavonoids of Dracocephalum moldavica can inhibit pyroptosis， thus exerting anti- pulmonary fibrosis effects.

Research progress of anti-pulmonary fibrosis drugs targeting autotaxin-lysophosphatidic acid axis / 药学学报

Pulmonary fibrosis is an interstitial lung disease characterized by inflammatory injury and tissue structure destruction. Currently, there is a lack of effective therapeutic drugs for pulmonary fibrosis, and the mechanism is still unknown. Therefore, it is urgent to seek new targets for effective drugs. In pulmonary fibrosis, the level of autotaxin (ATX) in bronchoalveolar lavage fluid increases and stimulates the production of lysophosphatidic acid (LPA). The involvement of LPA receptors in activating a variety of G-protein-mediated signal transduction pathways leads to a range of related physiological effects, including pro-inflammatory signaling in epithelial cells, activation of transforming growth factor signaling, and stimulation of fibroblast accumulation. LPA receptor antagonists and ATX inhibitors have been concerned as new targets for pulmonary fiber therapy, and currently related drugs have entered clinical trials. In this paper, the pathophysiological effects of LPA and ATX in pulmonary fibrosis disease and related drug development progress were reviewed to provide reference information of new drug development for pulmonary fibrosis based on the ATX-LPA axis.

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.

Effect of pirfenidone on paraquat-induced pulmonary fibrosis in rats / 中华劳动卫生职业病杂志

Objective: To construct paraquat (PQ) poisoning rat model and to explore the effect of pirfenidone (PFD) on PQ-induced pulmonary fibrosis. Methods: In April 2017, male 6-8 week-old Wistar rats were selected, and PQ was administered intraperitoneally at one time. PFD was administered by gavage 2 hours after poisoning. The daily gavage doses were 100, 200 and 300 mg/kg, and the rats were divided into physiological saline group, PQ group, PQ+PFD 100 group, PQ+PFD 200 group, PQ+PFD 300 group, with 10 rats in each group at each observation time point. The pathological changes of lung tissue at different time points (the 1st, 3rd, 7th, 14th, 28th, 42nd and 56th days) after poisoning and the effect of PFD intervention with different dose on PQ-induced pulmonary fibrosis were observed. Pathological evaluation of lung tissue was performed by Ashcroft scale method. The PQ+PFD 200 group was selected to further explore the pathological changes of lung tissue, the contents of hydroxyproline and malondialdehyde in lung tissue were determined.And the tumor necrosis factor (TNF) -α, interleukin (IL) -6, transforming growth factor (TGF) -β1, fibroblast growth factor (FGF) -B, platelet-derived growth factor (PDGF) -AB, insulin-like growth factor (IGF) -1 and PQ concentrations in serum and lung tissue were determined. Results: On the 1st to 7th day after PQ exposure, rats developed lung inflammation, which was aggravated on the 7th to 14th day, and pulmonary fibrosis appeared on the 14th to 56th day. Compared with PQ group, the Ashcroft scores of lung fibrosis in PQ+PFD 200 group and PQ+PDF 300 group decreased significantly in 7th and 28th day (P<0.05), while the Ashcroft score of lung fibrosis in PQ+PFD 100 group had no significant difference (P>0.05). After PQ exposure, the content of hydroxyproline in lung tissue increased gradually and reached the peak value on the 28th day. Compared with the PQ group, the contents of hydroxyproline in the PQ+PFD 200 group decreased at the 7th, 14th and 28th day, and the contents of malondialdehyde decreased at the 3rd and 7th day, the differences were statistically significant (P<0.05). The levels of TNF-α, IL-6 in rat serum and lung tissue reached the peak value on the 7th day after PQ exposure, and the levels of TGF-β1, FGF-B and IGF-1 in rat serum and lung tissue reached the peak value on the 14th day after PQ exposure, and the level of PDGF-AB in rat serum and lung tissue reached the peak value on the 28th day after PQ exposure. Compared with PQ group, the level of serum IL-6 in PQ+PFD 200 group decreased significantly on the 7th day, and serum TGF-β1, FGF-B, PDGF-AB and IGF-1 on the 14th and 28th day were decreased significantly (P<0.05). The levels of TNF-α, IL-6 in lung tissue of rats in PQ+PFD 200 group on the 7th day decreased significantly, and the levels of TGF-β1, FGF-B and IGF-1 in lung tissue of rats on the 14th day were significantly decreased, and the level of PDGF-AB in lung tissue of rats on the 28th day were significantly decreased (P<0.05) . Conclusion: PFD partially alleviates the PQ-induced lung inflammation and fibrosis by inhibiting oxidative stress, reducing the levels of pro-inflammatory and pro-fibrotic cytokines in serum and lung tissue, but does not affect the concentrations of PQ in serum and lung tissue.