Cell Mol Life Sci. 2021 Apr 17. doi: 10.1007/s00018-021-03841-7. Online ahead of print.

ABSTRACT

Mammalian lungs are metabolically active organs that frequently encounter environmental insults. Stress responses elicit protective autophagy in epithelial barrier cells and the supportive niche. Autophagy promotes the recycling of damaged intracellular organelles, denatured proteins, and other biological macromolecules for reuse as components required for lung cell survival. Autophagy, usually induced by metabolic defects, regulates cellular metabolism. Autophagy is a major adaptive response that protects cells and organisms from injury. Endogenous region-specific stem/progenitor cell populations are found in lung tissue, which are responsible for epithelial repair after lung damage. Additionally, glucose and fatty acid metabolism is altered in lung stem/progenitor cells in response to injury-related lung fibrosis. Autophagy deregulation has been observed to be involved in the development and progression of other respiratory diseases. This review explores the role and mechanisms of autophagy in regulating lung metabolism and epithelial repair.

PMID:33864479 | DOI:10.1007/s00018-021-03841-7

EBioMedicine. 2021 Apr 13;66:103325. doi: 10.1016/j.ebiom.2021.103325. Online ahead of print.

ABSTRACT

BACKGROUND: The transition from normal lung anatomy to minimal and established fibrosis is an important feature of the pathology of idiopathic pulmonary fibrosis (IPF). The purpose of this report is to examine the molecular and cellular mechanisms associated with this transition.

METHODS: Pre-operative thoracic Multidetector Computed Tomography (MDCT) scans of patients with severe IPF (n = 9) were used to identify regions of minimal(n = 27) and established fibrosis(n = 27). MDCT, Micro-CT, quantitative histology, and next-generation sequencing were used to compare 24 samples from donor controls (n = 4) to minimal and established fibrosis samples.

FINDINGS: The present results extended earlier reports about the transition from normal lung anatomy to minimal and established fibrosis by showing that there are activations of TGFBI, T cell co-stimulatory genes, and the down-regulation of inhibitory immune-checkpoint genes compared to controls. The expression patterns of these genes indicated activation of a field immune response, which is further supported by the increased infiltration of inflammatory immune cells dominated by lymphocytes that are capable of forming lymphoid follicles. Moreover, fibrosis pathways, mucin secretion, surfactant, TLRs, and cytokine storm-related genes also participate in the transitions from normal lung anatomy to minimal and established fibrosis.

INTERPRETATION: The transition from normal lung anatomy to minimal and established fibrosis is associated with genes that are involved in the tissue repair processes, the activation of immune responses as well as the increased infiltration of CD4, CD8, B cell lymphocytes, and macrophages. These molecular and cellular events correlate with the development of structural abnormality of IPF and probably contribute to its pathogenesis.

PMID:33862585 | DOI:10.1016/j.ebiom.2021.103325

Am J Respir Cell Mol Biol. 2021 Apr 16. doi: 10.1165/rcmb.2020-0279OC. Online ahead of print.

ABSTRACT

Strict control of iron homeostasis is critical for the maintenance of normal lung function. Iron accumulates in the lungs of patients with idiopathic pulmonary fibrosis (IPF), but the characteristics of iron metabolism in the pathogenesis of pulmonary fibrosis (PF) and related targeting therapeutics are not well studied. In this study, we investigated the cellular and molecular characteristics of iron metabolism in fibrotic lungs and further explored the efficacy of clioquinol (CQ) for the treatment of PF as well as its functional mechanism. Iron aggregates accumulated in the lungs of patients with IPF, and ferritin light chain (FTL) transcripts were increased in their pulmonary fibroblasts. In the bleomycin (BLM)-induced pulmonary fibrosis (BLM-PF) mouse model, pulmonary iron accumulation is a very early and concomitant event of PF. Labile iron pool (LIP) levels in both fibroblasts and macrophages from the BLM-PF model were elevated, and iron metabolism was dysregulated. CQ attenuated PF induced by BLM and fluorescein isothiocyanate (FITC), and iron-saturated clioquinol (ISCQ) did not alleviate BLM-PF. Furthermore, CQ inhibited the activation of fibroblasts, including proliferation, fibrotic differentiation, proinflammatory cytokine secretion and migration. In conclusion, our study demonstrated that CQ, acting as an iron chelator, attenuates experimental PF through inactivation of fibroblasts, providing support for targeting iron metabolism as a basis for PF treatment.

PMID:33861690 | DOI:10.1165/rcmb.2020-0279OC

Front Immunol. 2021 Mar 30;12:595811. doi: 10.3389/fimmu.2021.595811. eCollection 2021.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) differ in the predominant demographics and identified genetic risk alleles of effected patients, however both diseases frequently progress to respiratory failure and death. Contrasting advanced SSc-ILD to IPF provides insight to the role dysregulated immunity may play in pulmonary fibrosis. To analyze cell-type specific transcriptome commonalities and differences between IPF and SSc-ILD, we compared single-cell RNA-sequencing (scRNA-seq) of 21 explanted lung tissue specimens from patients with advanced IPF, SSc-ILD, and organ donor controls. Comparison of IPF and SSc-ILD tissue identified divergent patterns of interferon signaling, with interferon-gamma signaling upregulated in the SPP1 hi and FABP4 hi macrophages, cytotoxic T cells, and natural kill cells of IPF, while type I interferon signaling and production was upregulated in the corresponding SSc-ILD populations. Plasmacytoid dendritic cells were found in diseased lungs only, and exhibited upregulated cellular stress pathways in SSc-ILD compared to IPF. Alveolar type I cells were dramatically decreased in both IPF and SSc-ILD, with a distinct transcriptome signature separating these cells by disease. KRT5-/KRT17+ aberrant basaloid cells exhibiting markers of cellular senescence and epithelial-mesenchymal transition were identified in SSc-ILD for the first time. In summary, our study utilizes the enriched capabilities of scRNA-seq to identify key divergent cell types and pathways between IPF and SSc-ILD, providing new insights into the shared and distinct mechanisms between idiopathic and autoimmune interstitial lung diseases.

PMID:33859634 | PMC:PMC8042271 | DOI:10.3389/fimmu.2021.595811

Sci Rep. 2021 Apr 15;11(1):8312. doi: 10.1038/s41598-021-87747-1.

ABSTRACT

The clinical characteristics of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) differ from those of lung cancer in patients without IPF. Thus, we aimed to evaluate the impact of IPF on the clinical course of patients with lung cancer. Clinical data of IPF patients with lung cancer (n = 122) were compared with those of patients with lung cancer without IPF (n = 488) matched by age, sex, histopathology, stage, and date of diagnosis of lung cancer. The median follow-up period after diagnosis of lung cancer was 16 months. Among patients with IPF, the mean age was 68 years, 95.9% were male, 93.2% were ever-smokers, and squamous cell carcinoma was the most common cancer type (48.4%). The IPF group had poorer lung function and lower lobe predominance of lung cancer than the no-IPF group. The IPF group showed a poorer prognosis than the no-IPF group (5-year survival rate: 14.5% vs. 30.1%, respectively; P < 0.001), even after adjusting for lung function and regardless of the treatment method. Among patients with IPF, 16.8% experienced acute exacerbation within 1 month after treatment of lung cancer. The treatment outcome of patients with lung cancer and IPF was generally unfavorable, and acute exacerbation triggered by treatment frequently occurred.

PMID:33859288 | DOI:10.1038/s41598-021-87747-1

Thorax. 2021 Apr 15:thoraxjnl-2020-215962. doi: 10.1136/thoraxjnl-2020-215962. Online ahead of print.

ABSTRACT

RATIONALE: Extracellular vesicles (EVs) are small lipid vesicles, and EV-coupled microRNAs (miRNAs) are important modulators of biological processes. Fibrocytes are circulating bone marrow-derived cells that migrate into the injured lungs and contribute to fibrogenesis. The question of whether EV-coupled miRNAs derived from fibrocytes are able to regulate pulmonary fibrosis has not been addressed yet.

METHODS: Pulmonary fibrosis was induced in rats by intratracheal administration of an adenoviral gene vector encoding active transforming growth factor-β1 (TGF-β1) or control vector. Primary fibrocytes and fibroblasts were cultured from rat lungs and were sorted by anti-CD45 magnetic beads. Human circulating fibrocytes and fibrocytes in bronchoalveolar lavage fluid (BALF) were isolated by fibronectin-coated dishes. Fibrocytes were cultured on different stiffness plates or decellularised lung scaffolds. We also determined the effects of extracellular matrix (ECM) and recombinant TGF-β1 on the cellular and EV-coupled miRNA expression of fibrocytes.

RESULTS: The EVs of fibrocytes derived from fibrotic lungs significantly upregulated the expression of col1a1 of fibroblasts. Culturing on rigid plates or fibrotic decellularised lung scaffolds increased miR-21-5 p expression compared with soft plates or normal lung scaffolds. Dissolved ECM collected from fibrotic lungs and recombinant TGF-β1 increased miR-21-5 p expression on fibrocytes, and these effects were attenuated on soft plates. Fibrocytes from BALF collected from fibrotic interstitial pneumonia patients showed higher miR-21-5 p expression than those from other patients.

CONCLUSIONS: Our results indicate that ECM contributes to fibrogenesis through biomechanical and biochemical effects on miRNA expression in fibrocytes.

PMID:33859055 | DOI:10.1136/thoraxjnl-2020-215962

BMC Pulm Med. 2021 Apr 15;21(1):122. doi: 10.1186/s12890-021-01489-4.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with unclear pathogenesis. IPF is considered as a risk factor for lung cancer. Compared to other lung cancers, small-cell lung cancer (SCLC) has a lower incidence, but has a more aggressive course. Patients with IPF and SCLC have a lower survival rate, more difficult treatment, and poorer prognosis.

CASE PRESENTATION: Case 1 was of a 66-year-old man with IPF for 5 years, who was admitted to our hospital for dyspnea. Case 2 was of a 68-year-old woman, who presented with chest pains, cough, and dyspnea. Both patients had extremely poor lung function. High-resolution computed tomography and pathology revealed that both patients had IPF and SCLC. Chemotherapy comprising nedaplatin (80 mg/m2) and etoposide (100 mg for 5 days) was initiated for both patients. Antifibrotic agents were continued during the chemotherapeutic regimen. Both patients showed improvement in their condition after treatment.

CONCLUSION: The favorable outcomes in these 2 cases suggests that chemotherapy is worth considering in the management of patients having SCLC and IPF with poor lung function.

PMID:33858421 | DOI:10.1186/s12890-021-01489-4

Respiration. 2021 Apr 15:1-8. doi: 10.1159/000515182. Online ahead of print.

ABSTRACT

OBJECTIVE: Evaluation of software tools for segmentation, quantification, and characterization of fibrotic pulmonary parenchyma changes will strengthen the role of CT as biomarkers of disease extent, evolution, and response to therapy in idiopathic pulmonary fibrosis (IPF) patients.

METHODS: 418 nonenhanced thin-section MDCTs of 127 IPF patients and 78 MDCTs of 78 healthy individuals were analyzed through 3 fully automated, completely different software tools: YACTA, LUFIT, and IMBIO. The agreement between YACTA and LUFIT on segmented lung volume and 80th (reflecting fibrosis) and 40th (reflecting ground-glass opacity) percentile of the lung density histogram was analyzed using Bland-Altman plots. The fibrosis and ground-glass opacity segmented by IMBIO (lung texture analysis software tool) were included in specific regression analyses.

RESULTS: In the IPF-group, LUFIT outperformed YACTA by segmenting more lung volume (mean difference 242 mL, 95% limits of agreement -54 to 539 mL), as well as quantifying higher 80th (76 HU, -6 to 158 HU) and 40th percentiles (9 HU, -73 to 90 HU). No relevant differences were revealed in the control group. The 80th/40th percentile as quantified by LUFIT correlated positively with the percentage of fibrosis/ground-glass opacity calculated by IMBIO (r = 0.78/r = 0.92).

CONCLUSIONS: In terms of segmentation of pulmonary fibrosis, LUFIT as a shape model-based segmentation software tool is superior to the threshold-based YACTA, tool, since the density of (severe) fibrosis is similar to that of the surrounding soft tissues. Therefore, shape modeling as used in LUFIT may serve as a valid tool in the quantification of IPF, since this mainly affects the subpleural space.

PMID:33857945 | DOI:10.1159/000515182

Int Immunopharmacol. 2021 Apr 12;96:107608. doi: 10.1016/j.intimp.2021.107608. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease (ILD) that is marked by scarring of lung tissue, ultimately leading to respiratory failure. The survival rate of IPF is disappointing and to date demonstrates a clinical quandary. The exact etiology of the disease remains under discussion. According to the recent hypothesis, inflammatory mediators cause severe damage to the alveolar epithelium leading to the impairment of the alveolar structure. The role of inflammation in the development of the IPF has been controversial for years. There are two schools of thought regarding the role of inflammation. One group of researchers claims that cell death and fibroblast dysfunction are the primary causes and inflammation is just a secondary cause of IPF. The other group claims inflammation to be the primary cause. Studies using human subjects have also reported inflammation as a critical element in IPF. Inflammatory cytokinesserve amajor rolein commencing theinflammatoryresponse in the lungs. Several cytokines are reported to be involved in different molecular mechanisms underlying IPF, someof which alsocontribute additionally by acting as growth factors. The present review addressed to explore the contribution of various inflammatory cytokines, growth factors, and various other inflammatory molecules activating the major molecular pathways involved during the development of IPF.

PMID:33857801 | DOI:10.1016/j.intimp.2021.107608

Clin Rheumatol. 2021 Apr 15. doi: 10.1007/s10067-021-05732-5. Online ahead of print.

NO ABSTRACT

PMID:33856625 | DOI:10.1007/s10067-021-05732-5

J Cell Physiol. 2021 Apr 14. doi: 10.1002/jcp.30380. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a disease of progressive scarring caused by excessive extracellular matrix (ECM) deposition and activation of α-SMA-expressing myofibroblasts. Human antigen R (HuR) is an RNA binding protein that promotes protein translation. Upon translocation from the nucleus to the cytoplasm, HuR functions to stabilize messenger RNA (mRNA) to increase protein levels. However, the role of HuR in promoting ECM production, myofibroblast differentiation, and lung fibrosis is unknown. Human lung fibroblasts (HLFs) treated with transforming growth factor β1 (TGF-β1) showed a significant increase in translocation of HuR from the nucleus to the cytoplasm. TGF-β-treated HLFs that were transfected with HuR small interfering RNA had a significant reduction in α-SMA protein as well as the ECM proteins COL1A1, COL3A, and FN1. HuR was also bound to mRNA for ACTA2, COL1A1, COL3A1, and FN. HuR knockdown affected the mRNA stability of ACTA2 but not that of the ECM genes COL1A1, COL3A1, or FN. In mouse models of pulmonary fibrosis, there was higher cytoplasmic HuR in lung structural cells compared to control mice. In human IPF lungs, there was also more cytoplasmic HuR. This study is the first to show that HuR in lung fibroblasts controls their differentiation to myofibroblasts and consequent ECM production. Further research on HuR could assist in establishing the basis for the development of new target therapy for fibrotic diseases, such as IPF.

PMID:33855709 | DOI:10.1002/jcp.30380

J Cancer. 2021 Mar 14;12(10):2807-2814. doi: 10.7150/jca.51445. eCollection 2021.

ABSTRACT

Background: The incidence of idiopathic pulmonary fibrosis (IPF) and mortality related to the disease have steadily increased in recent years. The risk of cancer is approximately eight times higher in IPF patients than in the general population. The purpose of this study is to determine whether the severity of IPF is related to the time interval between IPF diagnosis and lung cancer diagnosis and to the stage of lung cancer at diagnosis. Methods: In this retrospective cohort study, we reviewed the medical records of patients with lung cancer after IPF diagnosis from two tertiary hospitals in South Korea between 2003 and 2018. We identified 61 patients diagnosed with lung cancer at least 3 months after being diagnosed with IPF. Results: The included patients had a mean age of 71.0 years, and all but one were men (98.4%). The interval between IPF diagnosis and lung cancer diagnosis was not related to the gender-age-physiology (GAP) stage (p=0.662). However, in cox proportional hazard models, a higher GAP stage was significantly correlated with an advanced lung cancer stage (odds ratio 11.1, p=0.003). Conclusions: The lung cancer stage at diagnosis was higher in patients with a higher GAP stage than in those with a lower GAP stage. Physicians should consider implementing more frequent surveillance with computed tomography scans for patients with advanced IPF.

PMID:33854581 | PMC:PMC8040885 | DOI:10.7150/jca.51445

Clin Med Insights Circ Respir Pulm Med. 2021 Mar 30;15:11795484211006050. doi: 10.1177/11795484211006050. eCollection 2021.

ABSTRACT

PURPOSE: Nintedanib is an approved treatment for idiopathic pulmonary fibrosis (IPF), which slows disease progression. Management of patients with IPF receiving nintedanib can be complicated by tolerability issues, comorbidities, and concomitant medications. We developed consensus recommendations on the management of dosing, adverse events and comorbidities in patients with IPF treated with nintedanib.

METHODS: A modified Delphi process using 3 questionnaires was used to survey 14 pulmonologists experienced in using nintedanib. Panelists rated their agreement with statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree). Consensus was predefined as a mean score of ⩽-2.5 or ⩾+2.5 with a standard deviation not crossing zero.

RESULTS: The panelists' recommendations were largely aligned with clinical trial data, real-world evidence, and the prescribing information, and provided additional guidance regarding minimizing gastrointestinal effects, periodic monitoring for liver dysfunction, caution with respect to concomitant administration of cytochrome P450 3A4 and P-glycoprotein 1 inhibitors and inducers and anticoagulants, and management of comorbidities. The panelists unanimously agreed that adverse event management should be individualized, based on careful consideration of the risks and benefits of each possible intervention and discussion with the patient.

CONCLUSIONS: These consensus recommendations provide additional guidance on the appropriate management of IPF with nintedanib, for use alongside evidence-based literature and the prescribing information.

PMID:33854398 | PMC:PMC8013629 | DOI:10.1177/11795484211006050

Acute Crit Care. 2021 Apr 15. doi: 10.4266/acc.2021.00073. Online ahead of print.

ABSTRACT

BACKGROUND: Acute exacerbation of interstitial lung disease (AE-ILD) causes clinically significant deterioration and has an extremely poor prognosis with high mortality. There are currently no demonstrated effective treatments. Recently, several studies reported the effectiveness of direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) in patients with AE-ILD as a potential therapy. This study describes the clinical effectiveness and safety of PMX-DHP in patients with AE-ILD.

METHODS: We retrospectively reviewed the medical records of 10 patients (11 episodes) with AE-ILD treated with PMX-DHP from January 2018 to June 2019. We compared laboratory and physiologic data of the ratio of partial pressure arterial oxygen to fraction of inspired oxygen (P/F ratio) and inflammatory markers before and after implementation of PMX-DHP.

RESULTS: Ten patients (11 episodes) were included according to the 2016 revised definition of acute exacerbation of idiopathic pulmonary fibrosis (IPF). Nine patients had IPF and one patient had fibrotic nonspecific interstitial pneumonia. Most patients (90.9%) were treated with a steroid pulse, and four patients (36.4%) were treated with an immunosuppressant. The median number of PMX-DHP cycles was 2, and the median duration of each cycle was 6 hours. After PMX-DHP, the mean P/F ratio improved (86 [range, 63-106] vs. 145 [86-260], P=0.030) and interleukin-6 and c-reactive protein decreased (79 [35-640] vs. 10 [5-25], P=0.018 and 14 [4-21] vs. 5 [2-6], P=0.019, respectively). The 30-day mortality rate was 27.3% and the 90-day mortality rate was 72.7%. There were no adverse events related to PMX-DHP treatment.

CONCLUSION: PMX-DHP treatment improved P/F ratio and reduced inflammatory markers in AE-ILD patients.

PMID:33853291 | DOI:10.4266/acc.2021.00073

Respiration. 2021 Apr 13:1-9. doi: 10.1159/000515335. Online ahead of print.

ABSTRACT

BACKGROUND: In idiopathic pulmonary fibrosis (IPF), some physiological parameters measured during a 6-min walk test (6-MWT) impart reliable prognostic information. Sit-to-stand tests (STSTs) are field exercise tests that are easier to implement than the 6-MWT in daily practice.

OBJECTIVES: The aims of the study were to test the reproducibility and compare 2 STSTs (the 1-min STST [1-STST] and the semi-paced 3-min chair rise test [3-CRT]) in IPF, and to determine if selected physiological parameters (speed of displacement and changes in pulse oxygen saturation [SpO2]) are interchangeable between the STSTs and the 6-MWT.

METHODS: Thirty-three patients with stable IPF were studied in 3 French expert centers. To test reproducibility, intra-class correlations (ICCs) of parameters measured during tests performed 7-14 days apart were calculated. To test interchangeability, the agreement and correlation of physiological responses measured during STSTs and during 6-MWT were studied.

RESULTS: Vertical displacements and changes in SpO2 during both STSTs were reproducible, with ICCs ranging from 0.78 [0.63-0.87] to 0.95 [0.92-0.97]. Vertical displacements during 1-STST and 3-CRT were correlated with 6-MWT distance (correlation coefficients (r) of 0.72 and 0.77, respectively; p < 0.001). Similarly, correlations were found between changes in SpO2 measured during the 2 STSTs and the 6-MWT, with coefficients ranging from 0.73 to 0.91 (p < 0.001). Distance walked and SpO2 during 6-MWT were well estimated from vertical displacement and SpO2 during the 2 STSTs, respectively.

CONCLUSION: The correlations found between the 2 STSTs and the 6-MWT suggest that STSTs may be of interest to assess displacement and exercise-induced changes in SpO2 in IPF patients.

PMID:33849043 | DOI:10.1159/000515335

Respiration. 2021 Apr 13:1-3. doi: 10.1159/000515665. Online ahead of print.

NO ABSTRACT

PMID:33849041 | DOI:10.1159/000515665

Respiration. 2021 Apr 13:1-2. doi: 10.1159/000515397. Online ahead of print.

NO ABSTRACT

PMID:33849033 | DOI:10.1159/000515397

Brief Bioinform. 2021 Apr 13:bbab115. doi: 10.1093/bib/bbab115. Online ahead of print.

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), better known as COVID-19, has become a current threat to humanity. The second wave of the SARS-CoV-2 virus has hit many countries, and the confirmed COVID-19 cases are quickly spreading. Therefore, the epidemic is still passing the terrible stage. Having idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are the risk factors of the COVID-19, but the molecular mechanisms that underlie IPF, COPD, and CVOID-19 are not well understood. Therefore, we implemented transcriptomic analysis to detect common pathways and molecular biomarkers in IPF, COPD, and COVID-19 that help understand the linkage of SARS-CoV-2 to the IPF and COPD patients. Here, three RNA-seq datasets (GSE147507, GSE52463, and GSE57148) from Gene Expression Omnibus (GEO) is employed to detect mutual differentially expressed genes (DEGs) for IPF, and COPD patients with the COVID-19 infection for finding shared pathways and candidate drugs. A total of 65 common DEGs among these three datasets were identified. Various combinatorial statistical methods and bioinformatics tools were used to build the protein-protein interaction (PPI) and then identified Hub genes and essential modules from this PPI network. Moreover, we performed functional analysis under ontologies terms and pathway analysis and found that IPF and COPD have some shared links to the progression of COVID-19 infection. Transcription factors-genes interaction, protein-drug interactions, and DEGs-miRNAs coregulatory network with common DEGs also identified on the datasets. We think that the candidate drugs obtained by this study might be helpful for effective therapeutic in COVID-19.

PMID:33847347 | DOI:10.1093/bib/bbab115

Front Pharmacol. 2021 Mar 18;12:644671. doi: 10.3389/fphar.2021.644671. eCollection 2021.

ABSTRACT

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.

PMID:33841163 | PMC:PMC8028140 | DOI:10.3389/fphar.2021.644671

Monaldi Arch Chest Dis. 2021 Apr 6. doi: 10.4081/monaldi.2021.1713. Online ahead of print.

ABSTRACT

Idiopathic pleuropulmonary fibroelastosis is an extremely rare lung disease characterized by the combination of fibrosis of the visceral pleura and the fibroelastotic changes transcending in the subpleural lung parenchyma that predominantly affects the upper lobes with accompanying volume loss. It is mostly idiopathic while infection, autoimmunity, bone marrow or lung transplantation and genetic predisposition may be associated with the development of PPFE. The disease is exceptionally rare as approximately ninety cases have been reported in the literature currently. A 35-year-old female presented with exertional dyspnea, dry cough and weight loss. Physical examination demonstrated platythorax, suprasternal notch deepening and fine rales over the upper lobes. Blood count, serum biochemistry, autoimmunity and serologic markers for collagen vascular diseases were within normal limits. Arterial blood gases demonstrated a low pO2 (48 mm Hg) and a high pCO2 (54 mm Hg) values. Chest x-ray showed bilateral parenchymal fibrotic lesions, left pneumothorax, bronchiectasis in the middle and pleural thickening in the upper lung zones while HRCT revealed bilateral apical pleural thickening, traction bronchiectasis, subpleural reticulations, ground-glass opacities and honeycombing in the upper lobes. Bronchoscopy, BAL cytology, smear and culture did not reveal any pathologic findings. Relevant with the clinical, laboratory, radiologic manifestations and the differential diagnosis with other interstitial lung diseases, PPFE was the final diagnosis. The aim of this case report was to present the clinical manifestations of our case. The second crucial objective was to establish a diagnostic scoring system relevant with the literature and the clinical manifestations of the patient.

PMID:33840184 | DOI:10.4081/monaldi.2021.1713