scholarly journals Hermansky-Pudlak Syndrome with Acute Hatred Idiopathic Pulmonary Fibrosis: All of the Patients of Oculocutaneous Albinism for Past 20 Years in Juntendo University Hospital

2021 ◽  
Author(s):  
YUKAKO KAGESHIMA ◽  
EIICHI INADA ◽  
KEN OKAMURA ◽  
TAMIO SUZUKI ◽  
MOTOYASU KATO ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Oculocutaneous Albinism ◽  
University Hospital ◽  
Hermansky Pudlak Syndrome

scholarly journals Hermansky-Pudlak Syndrome and Lung Disease: Pathogenesis and Therapeutics

2021 ◽  
Vol 12 ◽  
Author(s):  
Pamela Velázquez-Díaz ◽  
Erika Nakajima ◽  
Parand Sorkhdini ◽  
Ashley Hernandez-Gutierrez ◽  
Adam Eberle ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Molecular Mechanisms ◽  
Management Strategies ◽  
Oculocutaneous Albinism ◽  
Alveolar Epithelial Cells ◽  
Multisystem Disorder ◽  
Alveolar Epithelial ◽  
Novel Treatments ◽  
Molecular Approaches ◽  
Hermansky Pudlak Syndrome

Hermansky-Pudlak Syndrome (HPS) is a rare, genetic, multisystem disorder characterized by oculocutaneous albinism (OCA), bleeding diathesis, immunodeficiency, granulomatous colitis, and pulmonary fibrosis. HPS pulmonary fibrosis (HPS-PF) occurs in 100% of patients with subtype HPS-1 and has a similar presentation to idiopathic pulmonary fibrosis. Upon onset, individuals with HPS-PF have approximately 3 years before experiencing signs of respiratory failure and eventual death. This review aims to summarize current research on HPS along with its associated pulmonary fibrosis and its implications for the development of novel treatments. We will discuss the genetic basis of the disease, its epidemiology, and current therapeutic and clinical management strategies. We continue to review the cellular processes leading to the development of HPS-PF in alveolar epithelial cells, lymphocytes, mast cells, and fibrocytes, along with the molecular mechanisms that contribute to its pathogenesis and may be targeted in the treatment of HPS-PF. Finally, we will discuss emerging new cellular and molecular approaches for studying HPS, including lentiviral-mediated gene transfer, induced pluripotent stem cells (iPSCs), organoid and 3D-modelling, and CRISPR/Cas9-based gene editing approaches.

A rare diagnosis: Hermansky-Pudlak syndrome in a patient with pulmonary fibrosis, oculocutaneous albinism and thrombocytopathy

2019 ◽  
Author(s):  
Martina Doubková ◽  
Jakub Trizuljak ◽  
Anna Hrazdirová ◽  
Zuzana Vrzalová ◽  
Ivona Blaháková ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Oculocutaneous Albinism ◽  
Hermansky Pudlak Syndrome ◽  
Rare Diagnosis

scholarly journals Hermansky–Pudlak syndrome pulmonary fibrosis: a rare inherited interstitial lung disease

2021 ◽  
Vol 30 (159) ◽  
pp. 200193
Author(s):  
Tadafumi Yokoyama ◽  
Bernadette R. Gochuico
Keyword(s):  
Interstitial Lung Disease ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Genetic Diseases ◽  
Autosomal Recessive Disorder ◽  
Oculocutaneous Albinism ◽  
Excessive Bleeding ◽  
Lung Physiology ◽  
Hermansky Pudlak Syndrome ◽  
Fibrotic Lung Disease

Pulmonary fibrosis is a progressive interstitial lung disease of unknown aetiology with a poor prognosis. Studying genetic diseases associated with pulmonary fibrosis provides insights into the pathogenesis of the disease. Hermansky–Pudlak syndrome (HPS), a rare autosomal recessive disorder characterised by abnormal biogenesis of lysosome-related organelles, manifests with oculocutaneous albinism and excessive bleeding of variable severity. Pulmonary fibrosis is highly prevalent in three out of 10 genetic types of HPS (HPS-1, HPS-2 and HPS-4). Thus, genotyping of individuals with HPS is clinically relevant. HPS-1 tends to affect Puerto Rican individuals due to a genetic founder effect. HPS pulmonary fibrosis shares some clinical features with idiopathic pulmonary fibrosis (IPF), including dyspnoea, cough, restrictive lung physiology and computed tomography (CT) findings of fibrosis. In contrast to IPF, HPS pulmonary fibrosis generally affects children (HPS-2) or middle-aged adults (HPS-1 or HPS-4) and may be associated with ground-glass opacification in CT scans. Histopathology of HPS pulmonary fibrosis, and not IPF, shows vacuolated hyperplastic type II cells with enlarged lamellar bodies and alveolar macrophages with lipofuscin-like deposits. Antifibrotic drugs approved as treatment for IPF are not approved for HPS pulmonary fibrosis. However, lung transplantation has been performed in patients with severe HPS pulmonary fibrosis. HPS pulmonary fibrosis serves as a model for studying fibrotic lung disease and fibrosis in general.

scholarly journals Efficacy and safety of nintedanib in Japanese patients with early-stage idiopathic pulmonary fibrosis: a study protocol for an observational study

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e047249
Author(s):  
Noriho Sakamoto ◽  
Naoki Hamada ◽  
Masaki Okamoto ◽  
Kazunori Tobino ◽  
Hidenori Ichiyasu ◽  
...  
Keyword(s):  
Informed Consent ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Adverse Events ◽  
Study Protocol ◽  
Early Stage ◽  
Stage I ◽  
University Hospital ◽  
System Organ Class ◽  
Tolerability Profile

IntroductionIdiopathic pulmonary fibrosis (IPF) is a fibrotic disease of unknown aetiology with a poor prognosis. Several clinical trials of nintedanib in patients with IPF have reported its inhibitory effect on reduced lung function, incidence of acute exacerbation of IPF and worsened health-related quality of life. Although nintedanib has a manageable safety and tolerability profile over long-term use, it was discontinued in over 20% of patients because of adverse events such as diarrhoea and liver dysfunction. This might explain why nintedanib use in patients with IPF is not widespread, especially among patients with early-stage IPF. In the present study, we aimed to clarify the efficacy, safety and tolerability of nintedanib in patients with stage I/II IPF, based on the Japanese IPF disease severity staging classification system.Methods and analysisThis is an ongoing, prospective, multicentre observational cohort study of patients with stage I/II IPF who will start receiving nintedanib. Totally, 215 patients at 35 sites in Kyushu and Okinawa, Japan will be enrolled and followed up for 3 years. Nintedanib therapy would be initiated at the discretion of the investigator. The primary endpoint, change in forced vital capacity (FVC) at 156 weeks, will be shown as the mean change in FVC from baseline to week 156 with 95% CIs estimated using the Wald method. The safety endpoint—occurrence of adverse events—will be assessed in each system organ class/preferred term.Ethics and disseminationThe study protocol and informed consent documents were approved by the Institutional Review Board at Nagasaki University Hospital (approval number 19102146) and each participating site. Written informed consent was obtained from all participants. Patient recruitment has begun. The results will be disseminated through scientific peer-reviewed publications and national and international conferences.Trial registration numberUMIN000038192.

scholarly journals Benefit and clinical characteristics after the use of nintedanib in idiopathic pulmonary fibrosis

2019 ◽  
Vol 6 (2) ◽  
pp. 29-30
Author(s):  
Herrera-García José Carlos ◽  
Arellano Montellano Ek Ixel ◽  
Jaramillo Arellano Luis Enrique ◽  
Espinosa Arellano Andrea
Keyword(s):  
Lung Function ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Adverse Effects ◽  
Clinical Characteristics ◽  
Vital Capacity ◽  
University Hospital ◽  
Antifibrotic Therapy ◽  
Successful Case ◽  
Mexican Patient

Introduction: Nintedanib is an approved antifibrotic agent for the treatment of idiopathic pulmonary fibrosis. (FPI) as monotherapy. To date, the evidence supports its effectiveness in this type of patients. Methodology: We present the case of a Mexican patient of 69 years with Idiopathic Pulmonary Fibrosis (IPF) treated with nintedanib for 52 weeks as monotherapy in a university hospital. Results: Before the 52 week period. There was a clear decrease in the patient's forced vital capacity (FVC) from 70% (2.14L) to 60% (1.83L). The treatment with nintedanib was initiated for a period of 12 months at a dose of 150 mg VO every 12 hrs. Lung function stabilized increasing from 60% (1.83L) to 70% (2.14L), the treatment was well tolerated. Only with presence of mild adverse effects without repercussions. Conclusion: We describe the successful case of a patient with Idiopathic Pulmonary Fibrosis after 52 weeks of treatment with Nintedanib, well tolerated with improved lung function, until now the antifibrotic therapy represents a safe and therapeutically option as monotherapy.

scholarly journals Novel genetic variant of HPS1 gene in Hermansky-Pudlak syndrome with fulminant progression of pulmonary fibrosis: a case report

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Martina Doubková ◽  
Jakub Trizuljak ◽  
Zuzana Vrzalová ◽  
Anna Hrazdirová ◽  
Ivona Blaháková ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Clinical Manifestation ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Oculocutaneous Albinism ◽  
Differential Diagnostics ◽  
Compound Heterozygous ◽  
Carrier Status ◽  
Whole Exome ◽  
Hermansky Pudlak Syndrome

Abstract 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.

scholarly journals Hermansky-Pudlak syndrome with a novel genetic variant in HPS1 and subsequent accelerated pulmonary fibrosis: significance for phenocopy diseases

Thorax ◽  
2018 ◽  
Vol 73 (11) ◽  
pp. 1085-1088 ◽  
Author(s):  
Oliver J McElvaney ◽  
Marjan Huizing ◽  
William A Gahl ◽  
Paul O’Donovan ◽  
Deirdre Horan ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Genetic Diseases ◽  
Oculocutaneous Albinism ◽  
Bleeding Complications ◽  
Severe Bleeding ◽  
Autosomal Recessive Disorders ◽  
Dental Procedures ◽  
Hermansky Pudlak Syndrome ◽  
Biallelic Mutations ◽  
Recessive Disorders

The Hermansky-Pudlak syndrome (HPS) is a collection of autosomal-recessive disorders characterised by tyrosinase-positive oculocutaneous albinism (OCA), bleeding diatheses and, in selected individuals, early-onset accelerated pulmonary fibrosis, neutropaenia and granulomatous colitis. We describe a young man who presented following a self-directed literature review prompted by severe bleeding complications following minor surgical and dental procedures in the context of OCA. HPS was clinically suspected, with subsequent genetic testing confirming biallelic mutations in the HPS1 gene. Of interest, this is the only described HPS type 1 patient with two different (compound heterozygote) splice site variants in HPS1. In addition to detailing a novel genetic result and outlining the progressive clinical course of disease in this case, we discuss the management of HPS, the prognostic value of subtype analysis and the technical difficulties relating to transplantation in the case of HPS-associated advanced pulmonary fibrosis. This case also illustrates the concept of lung phenocopy relationships and the potential for elucidating the pathogenesis of more common pulmonary disorders by studying genetic diseases that result in similar phenotypes. Furthermore, it re-emphasises the importance of the patient voice, particularly with regard to complex diagnoses and rare diseases.

scholarly journals PD-L1 Expression in Patients with Idiopathic Pulmonary Fibrosis

2021 ◽  
Vol 10 (23) ◽  
pp. 5562
Author(s):  
Sissel Kronborg-White ◽  
Line Bille Madsen ◽  
Elisabeth Bendstrup ◽  
Venerino Poletti
Keyword(s):  
Epithelial Cells ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Smoking Status ◽  
Interstitial Lung Diseases ◽  
University Hospital ◽  
Malignant Neoplasms ◽  
Architectural Distortion ◽  
Mesenchymal Transition

Background: Idiopathic pulmonary fibrosis (IPF) is the most common and severe form within the group of idiopathic interstitial pneumonias. It is characterized by repetitive alveolar injury in genetically susceptible individuals and abnormal wound healing, leading to dysregulated bronchiolar proliferation and excessive deposition of extracellular matrix, causing complete architectural distortion and fibrosis. Epithelial-to-mesenchymal transition is considered an important pathogenic event, a phenomenon also observed in various malignant neoplasms, in which tumor cells express programmed death-ligand one (PD-L1). The aim of this study was to assess the presence of PD-L1 in patients with IPF and other interstitial lung diseases (ILDs). Method: Patients with a clinically and radiologically suspected idiopathic interstitial pneumonia or other ILDs undergoing transbronchial cryobiopsy to confirm the diagnosis at the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, were included in this prospective observational study. Cellular membrane PD-L1 expression in epithelial cells was determined using the DAKO PD-L1 IHC 22C3 PharmDx Kit. Results: Membrane-bound PD-L1 (mPD-L1) was found in twelve (28%) of the forty-three patients with IPF and in five (9%) of the fifty-five patients with other ILDs (p = 0.015). When adjusting for age, gender and smoking status, the odds ratio of having IPF when expressing mPD-L1 in alveolar and/or bronchiolar epithelial cells was 4.3 (CI: 1.3–14.3). Conclusion: Expression of mPD-L1 in epithelial cells in the lung parenchymal zones was detected in a consistent subgroup of patients with IPF compared to other interstitial pneumonias. Larger studies are needed to explore the role of mPD-L1 in patients with IPF.

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