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1.
Infect Dis Poverty ; 10(1): 31, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33731163

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a significant number of mortalities worldwide. COVID-19 poses a serious threat to human life. The clinical manifestations of COVID-19 are diverse and severe and 20% of infected patients are reported to be in a critical condition. A loss in lung function and pulmonary fibrosis are the main manifestations of patients with the severe form of the disease. The lung function is affected, even after recovery, thereby greatly affecting the psychology and well-being of patients, and significantly reducing their quality of life. METHODS: Participants must meet the following simultaneous inclusion criteria: over 18 years of age, should have recovered from severe or critical COVID-19 cases, should exhibit pulmonary fibrosis after recovery, and should exhibit Qi-Yin deficiency syndrome as indicated in the system of traditional Chinese medicine (TCM). The eligible candidates will be randomized into treatment or control groups. The treatment group will receive modern medicine (pirfenidone) plus TCM whereas the control group will be administered modern medicine plus TCM placebo. The lung function index will be continuously surveyed and recorded. By comparing the treatment effect between the two groups, the study intend to explore whether TCM can improve the effectiveness of modern medicine in patients with pulmonary fibrosis arising as a sequelae after SARS-CoV-2 infection. DISCUSSION: Pulmonary fibrosis is one of fatal sequelae for some severe or critical COVID-19 cases, some studies reveal that pirfenidone lead to a delay in the decline of forced expiratory vital capacity, thereby reducing the mortality partly. Additionally, although TCM has been proven to be efficacious in treating pulmonary fibrosis, its role in treating pulmonary fibrosis related COVID-19 has not been explored. Hence, a multicenter, parallel-group, randomized controlled, interventional, prospective clinical trial has been designed and will be conducted to determine if a new comprehensive treatment for pulmonary fibrosis related to COVID-19 is feasible and if it can improve the quality of life of patients. TRIAL REGISTRATION: This multicenter, parallel-group, randomized controlled, interventional, prospective trial was registered at the Chinese Clinical Trial Registry (ChiCTR2000033284) on 26th May 2020 (prospective registered).


Assuntos
/complicações , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/terapia , Antivirais/uso terapêutico , Terapia Combinada , Análise de Dados , Medicina Tradicional Chinesa , Fibrose Pulmonar/diagnóstico , Qualidade de Vida , Resultado do Tratamento
2.
PLoS One ; 16(3): e0248957, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33755708

RESUMO

The characteristics and evolution of pulmonary fibrosis in patients with coronavirus disease 2019 (COVID-19) have not been adequately studied. AI-assisted chest high-resolution computed tomography (HRCT) was used to investigate the proportion of COVID-19 patients with pulmonary fibrosis, the relationship between the degree of fibrosis and the clinical classification of COVID-19, the characteristics of and risk factors for pulmonary fibrosis, and the evolution of pulmonary fibrosis after discharge. The incidence of pulmonary fibrosis in patients with severe or critical COVID-19 was significantly higher than that in patients with moderate COVID-19. There were significant differences in the degree of pulmonary inflammation and the extent of the affected area among patients with mild, moderate and severe pulmonary fibrosis. The IL-6 level in the acute stage and albumin level were independent risk factors for pulmonary fibrosis. Ground-glass opacities, linear opacities, interlobular septal thickening, reticulation, honeycombing, bronchiectasis and the extent of the affected area were significantly improved 30, 60 and 90 days after discharge compared with at discharge. The more severe the clinical classification of COVID-19, the more severe the residual pulmonary fibrosis was; however, in most patients, pulmonary fibrosis was improved or even resolved within 90 days after discharge.


Assuntos
Inteligência Artificial , Fibrose Pulmonar/diagnóstico , Tórax/diagnóstico por imagem , /complicações , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Fibrose Pulmonar/etiologia , Fatores de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
3.
Respir Res ; 22(1): 38, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546680

RESUMO

Pulmonary fibrosis has been identified as a main factor leading to pulmonary dysfunction and poor quality of life in post-recovery Severe Acute Respiratory Syndrome (SARS) survivor's consequent to SARS-Cov-2 infection. Thus there is an urgent medical need for identification of readily available biomarkers that in patients with SARS-Cov-2 infection are able to; (1) identify patients in most need of medical care prior to admittance to an intensive care unit (ICU), and; (2) identify patients post-infection at risk of developing persistent fibrosis of lungs with subsequent impaired quality of life and increased morbidity and mortality. An intense amount of research have focused on wound healing and Extracellular Matrix (ECM) remodelling of the lungs related to lung function decline in pulmonary fibrosis (PF). A range of non-invasive serological biomarkers, reflecting tissue remodelling, and fibrosis have been shown to predict risk of acute exacerbations, lung function decline and mortality in PF and other interstitial lung diseases (Sand et al. in Respir Res 19:82, 2018). We suggest that lessons learned from such PF studies of the pathological processes leading to lung function decline could be used to better identify patients infected with SARS-Co-V2 at most risk of acute deterioration or persistent fibrotic damage of the lung and could consequently be used to guide treatment decisions.


Assuntos
/metabolismo , Matriz Extracelular/metabolismo , Fibrose Pulmonar/metabolismo , Cicatrização/fisiologia , Animais , Biomarcadores/metabolismo , Humanos , Pulmão/metabolismo , Fibrose Pulmonar/diagnóstico
4.
J Gene Med ; 23(3): e3318, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33533071

RESUMO

Pulmonary fibrosis is characterized by progressive and irreversible scarring in the lungs with poor prognosis and treatment. It is caused by various factors, including environmental and occupational exposures, and some rheumatic immune diseases. Even the rapid global spread of the COVID-19 pandemic can also cause pulmonary fibrosis with a high probability. Functions attributed to long non-coding RNAs (lncRNAs) make them highly attractive diagnostic and therapeutic targets in fibroproliferative diseases. Therefore, an understanding of the specific mechanisms by which lncRNAs regulate pulmonary fibrotic pathogenesis is urgently needed to identify new possibilities for therapy. In this review, we focus on the molecular mechanisms and implications of lncRNAs targeted protein-coding and non-coding genes during pulmonary fibrogenesis, and systematically analyze the communication of lncRNAs with various types of RNAs, including microRNA, circular RNA and mRNA. Finally, we propose the potential approach of lncRNA-based diagnosis and therapy for pulmonary fibrosis. We hope that understanding these interactions between protein-coding and non-coding genes will contribute to the development of lncRNA-based clinical applications for pulmonary fibrosis.


Assuntos
Marcadores Genéticos/genética , Fibrose Pulmonar/genética , RNA Longo não Codificante/genética , Regulação da Expressão Gênica , Terapia Genética/métodos , Humanos , MicroRNAs/genética , Proteínas/genética , Fibrose Pulmonar/diagnóstico , Fibrose Pulmonar/patologia , Fibrose Pulmonar/terapia , RNA Circular/genética
5.
Rheumatology (Oxford) ; 59(12): 3645-3656, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33313932

RESUMO

OBJECTIVES: Pleuroparenchymal fibroelastosis (PPFE) is characterized by predominantly upper lobe pleural and subjacent parenchymal fibrosis; PPFE features were described in patients with rheumatic autoimmune diseases (RAID). A systematic literature review was performed to investigate the prevalence, prognosis and potential association of PPFE with previous immunosuppression in RAID. METHODS: EMBASE, Web of Science and PubMed databases were questioned from inception to 1 September 2019. Articles published in English and addressing PPFE in patients with RAID were selected. RESULTS: Twenty out of 794 papers were selected with a total of 76 cases of RAID-PPFE patients (20 SSc, 9 RA, 6 IIM6 primary SS, 5 overlap syndromes, 3 ANCA-associated vasculitides, 2 granulomatosis with polyangiitis, 1 microscopic polyangiitis, 1 UCTD, 1 SLE, 1 GCA and 21 patients with non-specified RAID). Dyspnoea was the most frequently reported symptom (37/48 patients, 77%). Patients frequently presented with a restrictive pattern and decline in diffusing lung capacity for carbon monoxide. During the follow-up, 7/12 patients had progression at imaging, 22/39 presented a generic clinical worsening, 19/38 had a functional deterioration and 15/43 remained stable. CONCLUSION: The present systematic literature review confirms that PPFE features are present in RAID. Rheumatologists should be aware of this new radiological pattern that holds a bad prognosis.


Assuntos
Doenças Autoimunes/complicações , Doenças Pleurais/etiologia , Fibrose Pulmonar/etiologia , Doenças Reumáticas/complicações , Humanos , Doenças Pleurais/diagnóstico , Doenças Pleurais/terapia , Fibrose Pulmonar/diagnóstico , Fibrose Pulmonar/terapia , Doenças Reumáticas/imunologia
6.
J Toxicol Sci ; 45(10): 611-617, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33012729

RESUMO

Acute paraquat poisoning (APP) is a serious public health problem with a high mortality rate and there is no specific antidote for APP in clinical. Early haemoperfusion (HP) treatment is effective in APP rescue. In this study, we compared the influence of routine HP and continuous HP on the survival rate and the treatment of pulmonary fibrosis in mild and moderate APP patients. Eighty-two cases of mild and moderate APP patients who were admitted to our hospital from January of 2017 to December of 2018 were selected. All patients were randomly divided into a routine haemoperfusion (HP) group (n = 40) and a continuous haemoperfusion (CHP) group (n = 42). Compared with the HP group, the 28-day survival rate of mild and moderate APP patients was elevated in the CHP group. Blood N-terminal procollagen Ш propeptide (PIIINP) levels in APP patients were positively related with paraquat (PQ) concentration (r = 0.309, P = 0.000). There were statistically significant differences in the levels of PIIINP, Collage TypeIV (CIV), transforming growth factor-beta 1 (TGF-ß1), malondialdehyde (MDA), superoxide dismutase (SOD) activity and sequential organ failure assessment (SOFA) score between the two groups both on the third and seventh days after treatment, and the treatment effect of the CHP group on pulmonary fibrosis in APP patients was better than that of the HP group. In conclusion, CHP treatment had a significant therapeutic effect on mild and moderate APP patients, which could effectively improve the survival rate and relieve pulmonary fibrosis.


Assuntos
Hemoperfusão/métodos , Paraquat/envenenamento , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/terapia , Adolescente , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Fibrose Pulmonar/diagnóstico , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
7.
Sarcoidosis Vasc Diffuse Lung Dis ; 37(2): 231-233, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33093788

RESUMO

Background: A subgroup of patients with fibrotic ILD experience progression and several risk factors for ILD progression have been reported, such as male sex, older age, lower baseline pulmonary function, and a radiological or pathological pattern of usual interstitial pneumonia. Objective: To describe a possible new phenotype of rapidly non IPF progressive fibrosing with an IPF-like outcome. Methods: Three previously fit and well patients who developed a rapidly progressive ILD and died within 6 to 7 months from the initial development of respiratory symptoms. Results: Unlike what is currently known, our patients developed a severe fibrosing ILD with an IPF-like outcome despite a) being younger than the average patient with IPF, b) having received a non-IPF MDT diagnosis, c) having a non-UIP pattern on HRCT. Moreover and similarly to IPF, they failed to respond to immunosuppressive treatment which is the preferred treatment option in these cases. Conclusion: We believe that patients who present with similar characteristics should be considered as likely to develop a phenotype of rapidly progressive ILD and be treated with antifibrotic medications instead of immunosuppressive ones according to the favourable treatment response to antifibrotic therapy observed in clinical trials of patients with progressive fibrosing ILDs. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 231-233).


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico , Pulmão/diagnóstico por imagem , Fibrose Pulmonar/diagnóstico , Tomografia Computadorizada por Raios X , Adulto , Antibacterianos/uso terapêutico , Progressão da Doença , Evolução Fatal , Volume Expiratório Forçado , Humanos , Imunossupressores/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/fisiopatologia , Índice de Gravidade de Doença , Fatores de Tempo , Falha de Tratamento , Capacidade Vital
10.
Am J Respir Crit Care Med ; 202(3): e36-e69, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32706311

RESUMO

Background: This guideline addresses the diagnosis of hypersensitivity pneumonitis (HP). It represents a collaborative effort among the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.Methods: Systematic reviews were performed for six questions. The evidence was discussed, and then recommendations were formulated by a multidisciplinary committee of experts in the field of interstitial lung disease and HP using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.Results: The guideline committee defined HP, and clinical, radiographic, and pathological features were described. HP was classified into nonfibrotic and fibrotic phenotypes. There was limited evidence that was directly applicable to all questions. The need for a thorough history and a validated questionnaire to identify potential exposures was agreed on. Serum IgG testing against potential antigens associated with HP was suggested to identify potential exposures. For patients with nonfibrotic HP, a recommendation was made in favor of obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte cellular analysis, and suggestions for transbronchial lung biopsy and surgical lung biopsy were also made. For patients with fibrotic HP, suggestions were made in favor of obtaining BAL for lymphocyte cellular analysis, transbronchial lung cryobiopsy, and surgical lung biopsy. Diagnostic criteria were established, and a diagnostic algorithm was created by expert consensus. Knowledge gaps were identified as future research directions.Conclusions: The guideline committee developed a systematic approach to the diagnosis of HP. The approach should be reevaluated as new evidence accumulates.


Assuntos
Alveolite Alérgica Extrínseca/diagnóstico , Líquido da Lavagem Broncoalveolar/citologia , Exposição por Inalação , Pulmão/patologia , Linfócitos/imunologia , Fibrose Pulmonar/diagnóstico , Adulto , Alveolite Alérgica Extrínseca/complicações , Alveolite Alérgica Extrínseca/imunologia , Alveolite Alérgica Extrínseca/patologia , Biópsia , Broncoscopia , Criocirurgia , Humanos , Imunoglobulina G/imunologia , Anamnese , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/patologia , Testes Sorológicos , Inquéritos e Questionários
13.
Presse Med ; 49(2): 104021, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32437843

RESUMO

Interstitial lung diseases encompass a broad range of numerous individual conditions, some of them characterized histologically by fibrosis, especially idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, chronic hypersensitivity pneumonia, interstitial lung disease associated with connective tissue diseases, and unclassifiable interstitial lung disease. The diagnostic approach relies mainly on the clinical evaluation, especially assessment of the patient's demographics, history, smoking habits, occupational or domestic exposures, use of drugs, and on interpretation of high-quality HRCT of the chest. Imaging is key to the initial diagnostic approach, and often can confirm a definite diagnosis, particularly a diagnosis of idiopathic pulmonary fibrosis when showing a pattern of usual interstitial pneumonia in the appropriate context. In other cases, chest HRCT may orientate toward an alternative diagnosis and appropriate investigations to confirm the suspected diagnosis. Autoimmune serology helps diagnosing connective disease. Indications for bronchoalveolar lavage and for lung biopsy progressively become more restrictive, with better considerations for their discriminate value, of the potential risk associated with the procedure, and of the anticipated impact on management. Innovative techniques and genetics are beginning to contribute to diagnosing interstitial lung disease and to be implemented routinely in the clinic. Multidisciplinary discussion, enabling interaction between pulmonologists, chest radiologists, pathologists and often other healthcare providers, allows integration of all information available. It increases the accuracy of diagnosis and prognosis prediction, proposes a first-choice diagnosis, may suggest additional investigations, and often informs the management. The concept of working diagnosis, which can be revised upon additional information being made available especially longitudinal disease behaviour, helps dealing with diagnostic uncertainty inherent to interstitial lung diseases and facilitates management decisions. Above all, the clinical approach and how thoroughly the patient's history and possible exposures are assessed determine the possibility of an accurate diagnosis.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico , Alveolite Alérgica Extrínseca/diagnóstico , Doenças Autoimunes/diagnóstico , Biópsia , Lavagem Broncoalveolar , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/diagnóstico , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Pulmão/patologia , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/patologia , Exame Físico , Fibrose Pulmonar/diagnóstico , Radiografia Torácica , Testes de Função Respiratória , Tomografia Computadorizada por Raios X
15.
Ann Thorac Surg ; 110(1): e31-e33, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31926159

RESUMO

Characterized by pleural and subpleural fibrosis with alveolar septal elastosis, pleuroparenchymal fibroelastosis is a rare restrictive lung disease. Symptoms are often subtle, including dyspnea, cough, and weight loss; while acute presentations of spontaneous pneumothorax have been recorded. We report a patient who developed a spontaneous hemothorax, who upon evacuation of the chest was found to have a hemorrhagic lower lobe mass consistent with pleuroparenchymal fibroelastosis. Various conditions are associated with pleuroparenchymal fibroelastosis, suggesting chronic lung injury as a factor in pathogenesis. Hemothorax of this magnitude with relatively no known inciting risk factors, represents an exceptionally rare case presentation.


Assuntos
Hemotórax/etiologia , Pulmão/diagnóstico por imagem , Pleura/diagnóstico por imagem , Doenças Pleurais/complicações , Fibrose Pulmonar/complicações , Adulto , Biópsia , Fibrose/complicações , Fibrose/diagnóstico , Hemotórax/diagnóstico , Hemotórax/cirurgia , Humanos , Masculino , Doenças Pleurais/diagnóstico , Fibrose Pulmonar/diagnóstico , Toracoscopia , Tomografia Computadorizada por Raios X
17.
Pulmonology ; 26(1): 39-44, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31706882

RESUMO

In recent months two major fields of interest in pulmonary imaging have stood out: pulmonary fibrosis and pulmonary nodules. New guidelines have been released to define pulmonary fibrosis and subsequent studies have proved the value of these changes. In addition, new recommendations for classification of pulmonary nodules have been released. Radiological images are of major interest for automated and standardized analysis and so in both cases software tools using artificial intelligence were developed for visualization and quantification of the disease. These tools have been validated by human readers and demonstrated their capabilities. This review summarizes the new recommendations for classification of pulmonary fibrosis and nodules and reviews the capabilities of radiomics within these two entities.


Assuntos
Algoritmos , Inteligência Artificial , Neoplasias Pulmonares/diagnóstico , Pulmão/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/diagnóstico , Fibrose Pulmonar/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Humanos
18.
Arthritis Rheumatol ; 72(3): 465-476, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31682743

RESUMO

OBJECTIVE: To describe the associations between autoantibodies, clinical presentation, and outcomes among patients with systemic sclerosis (SSc) in order to develop a novel SSc classification scheme that would incorporate both antibodies and the cutaneous disease subset as criteria. METHODS: Demographic and clinical characteristics, including cutaneous subset, time of disease and organ complication onset, and autoantibody specificities, were determined in a cohort of SSc subjects. Survival analysis was used to assess the effect of the autoantibodies on organ disease and death. RESULTS: The study included 1,325 subjects. Among the antibody/skin disease subsets, anticentromere antibody-positive patients with limited cutaneous SSc (lcSSc) (n = 374) had the highest 20-year survival (65.3%), lowest incidence of clinically significant pulmonary fibrosis (PF) (8.5%) and scleroderma renal crisis (SRC) (0.3%), and lowest incidence of cardiac SSc (4.9%), whereas the frequency of pulmonary hypertension (PH) was similar to the mean value in the SSc cohort overall. The anti-Scl-70+ groups of patients with lcSSc (n = 138) and patients with diffuse cutaneous SSc (dcSSc) (n = 149) had the highest incidence of clinically significant PF (86.1% and 84%, respectively, at 15 years). Anti-Scl-70+ patients with dcSSc had the lowest survival (32.4%) and the second highest incidence of cardiac SSc (12.9%) at 20 years. In contrast, in anti-Scl-70+ patients with lcSSc, other complications were rare, and these patients demonstrated the lowest incidence of PH (6.9%) and second highest survival (61.8%) at 20 years. Anti-RNA polymerase antibody-positive SSc patients (n = 147) had the highest incidence of SRC (28.1%) at 20 years. The anti-U3 RNP+ SSc group (n = 56) had the highest incidence of PH (33.8%) and cardiac SSc (13.2%) at 20 years. Among lcSSc patients with other autoantibodies (n = 295), the risk of SRC and cardiac SSc was low at 20 years (2.7% and 2.4%, respectively), while the frequencies of other outcomes were similar to the mean values in the full SSc cohort. Patients with dcSSc who were positive for other autoantibodies (n = 166) had a poor prognosis, demonstrating the second lowest survival (33.6%) and frequent organ complications. CONCLUSION: These findings highlight the importance of autoantibodies, cutaneous subset, and disease duration when assessing morbidity and mortality in patients with SSc. Our novel classification scheme may improve disease monitoring and benefit future clinical trial designs in SSc.


Assuntos
Autoanticorpos/sangue , Avaliação de Resultados em Cuidados de Saúde/classificação , Fibrose Pulmonar/classificação , Esclerodermia Difusa/classificação , Escleroderma Sistêmico/classificação , Adulto , Anticorpos Antinucleares/sangue , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/diagnóstico , Fibrose Pulmonar/mortalidade , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/mortalidade , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/mortalidade , Pele/patologia , Análise de Sobrevida
20.
BMC Pulm Med ; 19(1): 178, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619213

RESUMO

BACKGROUND: Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that is associated with oculocutaneous albinism, bleeding diathesis, granulomatous colitis, and highly penetrant pulmonary fibrosis in some subtypes. Homozygous or compound heterozygous pathological variants in HPS1, HPS3, HPS4, and several other genes lead to clinical manifestation of the disease. CASE PRESENTATION: A 57-year-old female was admitted with congenital oculocutaneous albinism, thrombocytopathy and late-onset accelerated pulmonary fibrosis (first symptoms from age 50 onwards). Chest high-resolution computed tomography identified thickening of peribronchovascular interstitium, bronchiectasis, reticulations, honeycombing, ground glass opacities and lung parenchyma consolidations. HPS was clinically suspected. We performed whole exome sequencing (WES), a form of massive parallel sequencing, of proband-parents trio. Whole exome libraries were processed using KAPA Hyper Prep Kit, SeqCap EZ MedExome Enrichment Kit and HyperCap Bead Kit according to the SeqCap EZ HyperCap Workflow. The paired-end 2 × 75 bp sequencing was performed on the Illumina NextSeq 500 Sequencer (Illumina Inc., USA). Furthermore, obtained variants by WES were evaluated using a virtual panel of genes: HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1, BLOC1S3, and PLDN. We identified a compound heterozygous genotype in HPS1 gene in the proband. We identified a pathogenic frameshift variant c.1189delC; p.(Gln397Serfs*2), resulting in a premature stop codon. This variant has been previously associated with HPS. Furthermore, we characterized previously undescribed nonsense variant c.1507C > T; p.(Gln503*), resulting in a premature stop codon and mRNA degradation through nonsense-mediated decay. Sanger sequencing validated the presence of both variants and simultaneously confirmed the heterozygous carrier status of parents. Unfortunately, the patient died due to fulminant progression of pulmonary fibrosis 2 months after diagnostics. CONCLUSIONS: Compound heterozygous mutations in HPS1 in the proband lead to disruption of HPS1 gene and clinical manifestation of HPS with severe pulmonary fibrosis. This case illustrates the need to consider HPS in differential diagnostics of pulmonary fibrosis. Pulmonary fibrosis is a common cause of death in HPS patients. Earlier diagnosis may enable better treatment for these patients.


Assuntos
Síndrome de Hermanski-Pudlak , Pulmão/diagnóstico por imagem , Proteínas de Membrana/genética , Fibrose Pulmonar , Progressão da Doença , Evolução Fatal , Feminino , Síndrome de Hermanski-Pudlak/diagnóstico , Síndrome de Hermanski-Pudlak/genética , Síndrome de Hermanski-Pudlak/fisiopatologia , Humanos , Pulmão/patologia , Pessoa de Meia-Idade , Mutação , Fibrose Pulmonar/diagnóstico , Fibrose Pulmonar/genética , Fibrose Pulmonar/fisiopatologia , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos , Sequenciamento Completo do Exoma/métodos
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